Tumor cell plasticity, heterogeneity, and resistance in crucial microenvironmental niches in glioma
Both the perivascular niche (PVN) and the integration into multicellular networks by tumor microtubes (TMs) have been associated with progression and resistance to therapies in glioblastoma, but their specific contribution remained unknown. By long-term tracking of tumor cell fate and dynamics in th...
Ausführliche Beschreibung
Gespeichert in:
| Autor*in: |
Jung, Erik [verfasserIn] Osswald, Matthias - 1982- [verfasserIn] Ratliff, Miriam - 1979- [verfasserIn] Dogan, Helin - 1999- [verfasserIn] Xie, Ruifan [verfasserIn] Heuer, Sophie - 1992- [verfasserIn] Hoffmann, Dirk C. - 1992- [verfasserIn] Kurz, Felix T. - 1981- [verfasserIn] Keßler, Tobias - 1987- [verfasserIn] Heiland, Sabine [verfasserIn] Deimling, Andreas von - 1959- [verfasserIn] Sahm, Felix - 1984- [verfasserIn] Wick, Wolfgang - 1970- [verfasserIn] Winkler, Frank - 1971- [verfasserIn] |
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| Format: |
E-Artikel |
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| Sprache: |
Englisch |
| Erschienen: |
12 February 2021 |
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| Anmerkung: |
Gesehen am 19.04.2021 |
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| Umfang: |
16 |
| Übergeordnetes Werk: |
Enthalten in: Nature Communications - [London] : Springer Nature, 2010, 12(2021), Artikel-ID 1014, Seite 1-16 |
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| Übergeordnetes Werk: |
volume:12 ; year:2021 ; elocationid:1014 ; pages:1-16 ; extent:16 |
| Links: |
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| DOI / URN: |
10.1038/s41467-021-21117-3 |
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| Katalog-ID: |
1755371330 |
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| 245 | 1 | 0 | |a Tumor cell plasticity, heterogeneity, and resistance in crucial microenvironmental niches in glioma |c Erik Jung, Matthias Osswald, Miriam Ratliff, Helin Dogan, Ruifan Xie, Sophie Weil, Dirk C. Hoffmann, Felix T. Kurz, Tobias Kessler, Sabine Heiland, Andreas von Deimling, Felix Sahm, Wolfgang Wick and Frank Winkler |
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| 520 | |a Both the perivascular niche (PVN) and the integration into multicellular networks by tumor microtubes (TMs) have been associated with progression and resistance to therapies in glioblastoma, but their specific contribution remained unknown. By long-term tracking of tumor cell fate and dynamics in the live mouse brain, differential therapeutic responses in both niches are determined. Both the PVN, a preferential location of long-term quiescent glioma cells, and network integration facilitate resistance against cytotoxic effects of radiotherapy and chemotherapy—independently of each other, but with additive effects. Perivascular glioblastoma cells are particularly able to actively repair damage to tumor regions. Population of the PVN and resistance in it depend on proficient NOTCH1 expression. In turn, NOTCH1 downregulation induces resistant multicellular networks by TM extension. Our findings identify NOTCH1 as a central switch between the PVN and network niche in glioma, and demonstrate robust cross-compensation when only one niche is targeted. | ||
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10.1038/s41467-021-21117-3 doi (DE-627)1755371330 (DE-599)KXP1755371330 (OCoLC)1341405012 DE-627 ger DE-627 rda eng Jung, Erik verfasserin (DE-588)1160204640 (DE-627)1023329875 (DE-576)505549409 aut Tumor cell plasticity, heterogeneity, and resistance in crucial microenvironmental niches in glioma Erik Jung, Matthias Osswald, Miriam Ratliff, Helin Dogan, Ruifan Xie, Sophie Weil, Dirk C. Hoffmann, Felix T. Kurz, Tobias Kessler, Sabine Heiland, Andreas von Deimling, Felix Sahm, Wolfgang Wick and Frank Winkler 12 February 2021 16 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Gesehen am 19.04.2021 Both the perivascular niche (PVN) and the integration into multicellular networks by tumor microtubes (TMs) have been associated with progression and resistance to therapies in glioblastoma, but their specific contribution remained unknown. By long-term tracking of tumor cell fate and dynamics in the live mouse brain, differential therapeutic responses in both niches are determined. Both the PVN, a preferential location of long-term quiescent glioma cells, and network integration facilitate resistance against cytotoxic effects of radiotherapy and chemotherapy—independently of each other, but with additive effects. Perivascular glioblastoma cells are particularly able to actively repair damage to tumor regions. Population of the PVN and resistance in it depend on proficient NOTCH1 expression. In turn, NOTCH1 downregulation induces resistant multicellular networks by TM extension. Our findings identify NOTCH1 as a central switch between the PVN and network niche in glioma, and demonstrate robust cross-compensation when only one niche is targeted. Osswald, Matthias 1982- verfasserin (DE-588)139015620 (DE-627)703181645 (DE-576)309419069 aut Ratliff, Miriam 1979- verfasserin (DE-588)1012081028 (DE-627)660894602 (DE-576)344899357 aut Dogan, Helin 1999- verfasserin (DE-588)1298521866 (DE-627)1854494619 aut Xie, Ruifan verfasserin (DE-588)1153554720 (DE-627)1015049419 (DE-576)500293449 aut Heuer, Sophie 1992- verfasserin (DE-588)1164511882 (DE-627)1028945574 (DE-576)510060609 aut Hoffmann, Dirk C. 1992- verfasserin (DE-588)1231940786 (DE-627)1755605366 aut Kurz, Felix T. 1981- verfasserin (DE-588)1043285474 (DE-627)771321066 (DE-576)394610342 aut Keßler, Tobias 1987- verfasserin (DE-588)1104151693 (DE-627)86164591X (DE-576)470840277 aut Heiland, Sabine verfasserin (DE-588)106732626X (DE-627)818624450 (DE-576)426561368 aut Deimling, Andreas von 1959- verfasserin (DE-588)103034115X (DE-627)735093946 (DE-576)378138065 aut Sahm, Felix 1984- verfasserin (DE-588)1022852132 (DE-627)717318478 (DE-576)366075020 aut Wick, Wolfgang 1970- verfasserin (DE-588)120297736 (DE-627)080586929 (DE-576)186221320 aut Winkler, Frank 1971- verfasserin (DE-588)120794586 (DE-627)704993104 (DE-576)292388586 aut Enthalten in Nature Communications [London] : Springer Nature, 2010 12(2021), Artikel-ID 1014, Seite 1-16 Online-Ressource (DE-627)626457688 (DE-600)2553671-0 (DE-576)331555905 2041-1723 nnns volume:12 year:2021 elocationid:1014 pages:1-16 extent:16 https://doi.org/10.1038/s41467-021-21117-3 Verlag Resolving-System kostenfrei Volltext https://www.nature.com/articles/s41467-021-21117-3 Verlag kostenfrei Volltext GBV_USEFLAG_U GBV_ILN_2011 ISIL_DE-16 SYSFLAG_1 GBV_KXP GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_211 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_2014 GBV_ILN_2110 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4335 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 GBV_ILN_2013 GBV_ILN_2403 GBV_ILN_2013 ISIL_DE-16-250 GBV_ILN_2403 ISIL_DE-LFER AR 12 2021 1014 1-16 16 2011 01 DE-16 4291940599 00 --%%-- --%%-- --%%-- --%%-- l01 17-03-23 2013 01 DE-16-250 3913380442 00 --%%-- --%%-- --%%-- --%%-- l01 19-04-21 2403 01 DE-LFER 4319023765 00 --%%-- --%%-- n --%%-- l01 08-05-23 2403 01 DE-LFER https://doi.org/10.1038/s41467-021-21117-3 2403 01 DE-LFER https://www.nature.com/articles/s41467-021-21117-3 2013 01 DE-16-250 00 s hd2021 2013 01 DE-16-250 01 s (DE-627)1410508463 wissenschaftlicher Artikel (Zeitschrift) 2013 01 DE-16-250 02 s per_14 2013 01 DE-16-250 03 s s_16 2013 01 DE-16-250 04 p (DE-627)1580061443 Jung, Erik 2013 01 DE-16-250 04 k (DE-627)1416741267 Neurologische Universitätsklinik 2013 01 DE-16-250 04 s (DE-627)1410501914 Verfasser 2013 01 DE-16-250 04 s pos_1 2013 01 DE-16-250 05 p (DE-627)1477516328 Osswald, Matthias 2013 01 DE-16-250 05 k (DE-627)1416822720 Extern 2013 01 DE-16-250 05 s (DE-627)1410501914 Verfasser 2013 01 DE-16-250 05 s pos_ 2 2013 01 DE-16-250 06 p (DE-627)1499428073 Ratliff, Miriam 2013 01 DE-16-250 06 k (DE-627)1426595700 Neurochirurgische Klinik 2013 01 DE-16-250 06 s (DE-627)1410501914 Verfasser 2013 01 DE-16-250 06 s pos_3 2013 01 DE-16-250 07 p (DE-627)1854494929 Dogan, Helin 2013 01 DE-16-250 07 k (DE-627)1416466967 Medizinische Fakultät Heidelberg 2013 01 DE-16-250 07 s (DE-627)1410501914 Verfasser 2013 01 DE-16-250 07 s pos_4 2013 01 DE-16-250 08 p (DE-627)1574264605 Xie, Ruifan 2013 01 DE-16-250 08 k (DE-627)1416822720 Extern 2013 01 DE-16-250 08 s (DE-627)1410501914 Verfasser 2013 01 DE-16-250 08 s pos_ 5 2013 01 DE-16-250 09 p (DE-627)1580061478 Heuer, Sophie 2013 01 DE-16-250 09 k (DE-627)1416741267 Neurologische Universitätsklinik 2013 01 DE-16-250 09 s (DE-627)1410501914 Verfasser 2013 01 DE-16-250 09 s pos_6 2013 01 DE-16-250 10 p (DE-627)1755605471 Hoffmann, Dirk C. 2013 01 DE-16-250 10 k (DE-627)1416741267 Neurologische Universitätsklinik 2013 01 DE-16-250 10 s (DE-627)1410501914 Verfasser 2013 01 DE-16-250 10 s pos_7 2013 01 DE-16-250 11 p (DE-627)1515419355 Kurz, Felix T. 2013 01 DE-16-250 11 k (DE-627)1416741267 Neurologische Universitätsklinik 2013 01 DE-16-250 11 k (DE-627)1416466967 Medizinische Fakultät Heidelberg 2013 01 DE-16-250 11 s (DE-627)1410501914 Verfasser 2013 01 DE-16-250 11 s pos_ 8 2013 01 DE-16-250 12 p (DE-627)1547668547 Keßler, Tobias 2013 01 DE-16-250 12 k (DE-627)1416741267 Neurologische Universitätsklinik 2013 01 DE-16-250 12 s (DE-627)1410501914 Verfasser 2013 01 DE-16-250 12 s pos_ 9 2013 01 DE-16-250 13 p (DE-627)1496564405 Heiland, Sabine 2013 01 DE-16-250 13 k (DE-627)1416741267 Neurologische Universitätsklinik 2013 01 DE-16-250 13 s (DE-627)1410501914 Verfasser 2013 01 DE-16-250 13 s pos_ 10 2013 01 DE-16-250 14 p (DE-627)1448137985 Deimling, Andreas von 2013 01 DE-16-250 14 k (DE-627)1416741658 Pathologisches Institut 2013 01 DE-16-250 14 s (DE-627)1410501914 Verfasser 2013 01 DE-16-250 14 s pos_ 11 2013 01 DE-16-250 15 p (DE-627)143607634X Sahm, Felix 2013 01 DE-16-250 15 k (DE-627)1416741658 Pathologisches Institut 2013 01 DE-16-250 15 k (DE-627)1416466967 Medizinische Fakultät Heidelberg 2013 01 DE-16-250 15 s (DE-627)1410501914 Verfasser 2013 01 DE-16-250 15 s pos_ 12 2013 01 DE-16-250 16 p (DE-627)1450189326 Wick, Wolfgang 2013 01 DE-16-250 16 k (DE-627)1416741267 Neurologische Universitätsklinik 2013 01 DE-16-250 16 s (DE-627)1410501914 Verfasser 2013 01 DE-16-250 16 s pos_ 13 2013 01 DE-16-250 17 p (DE-627)1477506500 Winkler, Frank 2013 01 DE-16-250 17 k (DE-627)1416741267 Neurologische Universitätsklinik 2013 01 DE-16-250 17 s (DE-627)1410501914 Verfasser 2013 01 DE-16-250 17 s pos_ 14 |
| spelling |
10.1038/s41467-021-21117-3 doi (DE-627)1755371330 (DE-599)KXP1755371330 (OCoLC)1341405012 DE-627 ger DE-627 rda eng Jung, Erik verfasserin (DE-588)1160204640 (DE-627)1023329875 (DE-576)505549409 aut Tumor cell plasticity, heterogeneity, and resistance in crucial microenvironmental niches in glioma Erik Jung, Matthias Osswald, Miriam Ratliff, Helin Dogan, Ruifan Xie, Sophie Weil, Dirk C. Hoffmann, Felix T. Kurz, Tobias Kessler, Sabine Heiland, Andreas von Deimling, Felix Sahm, Wolfgang Wick and Frank Winkler 12 February 2021 16 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Gesehen am 19.04.2021 Both the perivascular niche (PVN) and the integration into multicellular networks by tumor microtubes (TMs) have been associated with progression and resistance to therapies in glioblastoma, but their specific contribution remained unknown. By long-term tracking of tumor cell fate and dynamics in the live mouse brain, differential therapeutic responses in both niches are determined. Both the PVN, a preferential location of long-term quiescent glioma cells, and network integration facilitate resistance against cytotoxic effects of radiotherapy and chemotherapy—independently of each other, but with additive effects. Perivascular glioblastoma cells are particularly able to actively repair damage to tumor regions. Population of the PVN and resistance in it depend on proficient NOTCH1 expression. In turn, NOTCH1 downregulation induces resistant multicellular networks by TM extension. Our findings identify NOTCH1 as a central switch between the PVN and network niche in glioma, and demonstrate robust cross-compensation when only one niche is targeted. Osswald, Matthias 1982- verfasserin (DE-588)139015620 (DE-627)703181645 (DE-576)309419069 aut Ratliff, Miriam 1979- verfasserin (DE-588)1012081028 (DE-627)660894602 (DE-576)344899357 aut Dogan, Helin 1999- verfasserin (DE-588)1298521866 (DE-627)1854494619 aut Xie, Ruifan verfasserin (DE-588)1153554720 (DE-627)1015049419 (DE-576)500293449 aut Heuer, Sophie 1992- verfasserin (DE-588)1164511882 (DE-627)1028945574 (DE-576)510060609 aut Hoffmann, Dirk C. 1992- verfasserin (DE-588)1231940786 (DE-627)1755605366 aut Kurz, Felix T. 1981- verfasserin (DE-588)1043285474 (DE-627)771321066 (DE-576)394610342 aut Keßler, Tobias 1987- verfasserin (DE-588)1104151693 (DE-627)86164591X (DE-576)470840277 aut Heiland, Sabine verfasserin (DE-588)106732626X (DE-627)818624450 (DE-576)426561368 aut Deimling, Andreas von 1959- verfasserin (DE-588)103034115X (DE-627)735093946 (DE-576)378138065 aut Sahm, Felix 1984- verfasserin (DE-588)1022852132 (DE-627)717318478 (DE-576)366075020 aut Wick, Wolfgang 1970- verfasserin (DE-588)120297736 (DE-627)080586929 (DE-576)186221320 aut Winkler, Frank 1971- verfasserin (DE-588)120794586 (DE-627)704993104 (DE-576)292388586 aut Enthalten in Nature Communications [London] : Springer Nature, 2010 12(2021), Artikel-ID 1014, Seite 1-16 Online-Ressource (DE-627)626457688 (DE-600)2553671-0 (DE-576)331555905 2041-1723 nnns volume:12 year:2021 elocationid:1014 pages:1-16 extent:16 https://doi.org/10.1038/s41467-021-21117-3 Verlag Resolving-System kostenfrei Volltext https://www.nature.com/articles/s41467-021-21117-3 Verlag kostenfrei Volltext GBV_USEFLAG_U GBV_ILN_2011 ISIL_DE-16 SYSFLAG_1 GBV_KXP GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_211 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_2014 GBV_ILN_2110 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4335 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 GBV_ILN_2013 GBV_ILN_2403 GBV_ILN_2013 ISIL_DE-16-250 GBV_ILN_2403 ISIL_DE-LFER AR 12 2021 1014 1-16 16 2011 01 DE-16 4291940599 00 --%%-- --%%-- --%%-- --%%-- l01 17-03-23 2013 01 DE-16-250 3913380442 00 --%%-- --%%-- --%%-- --%%-- l01 19-04-21 2403 01 DE-LFER 4319023765 00 --%%-- --%%-- n --%%-- l01 08-05-23 2403 01 DE-LFER https://doi.org/10.1038/s41467-021-21117-3 2403 01 DE-LFER https://www.nature.com/articles/s41467-021-21117-3 2013 01 DE-16-250 00 s hd2021 2013 01 DE-16-250 01 s (DE-627)1410508463 wissenschaftlicher Artikel (Zeitschrift) 2013 01 DE-16-250 02 s per_14 2013 01 DE-16-250 03 s s_16 2013 01 DE-16-250 04 p (DE-627)1580061443 Jung, Erik 2013 01 DE-16-250 04 k (DE-627)1416741267 Neurologische Universitätsklinik 2013 01 DE-16-250 04 s (DE-627)1410501914 Verfasser 2013 01 DE-16-250 04 s pos_1 2013 01 DE-16-250 05 p (DE-627)1477516328 Osswald, Matthias 2013 01 DE-16-250 05 k (DE-627)1416822720 Extern 2013 01 DE-16-250 05 s (DE-627)1410501914 Verfasser 2013 01 DE-16-250 05 s pos_ 2 2013 01 DE-16-250 06 p (DE-627)1499428073 Ratliff, Miriam 2013 01 DE-16-250 06 k (DE-627)1426595700 Neurochirurgische Klinik 2013 01 DE-16-250 06 s (DE-627)1410501914 Verfasser 2013 01 DE-16-250 06 s pos_3 2013 01 DE-16-250 07 p (DE-627)1854494929 Dogan, Helin 2013 01 DE-16-250 07 k (DE-627)1416466967 Medizinische Fakultät Heidelberg 2013 01 DE-16-250 07 s (DE-627)1410501914 Verfasser 2013 01 DE-16-250 07 s pos_4 2013 01 DE-16-250 08 p (DE-627)1574264605 Xie, Ruifan 2013 01 DE-16-250 08 k (DE-627)1416822720 Extern 2013 01 DE-16-250 08 s (DE-627)1410501914 Verfasser 2013 01 DE-16-250 08 s pos_ 5 2013 01 DE-16-250 09 p (DE-627)1580061478 Heuer, Sophie 2013 01 DE-16-250 09 k (DE-627)1416741267 Neurologische Universitätsklinik 2013 01 DE-16-250 09 s (DE-627)1410501914 Verfasser 2013 01 DE-16-250 09 s pos_6 2013 01 DE-16-250 10 p (DE-627)1755605471 Hoffmann, Dirk C. 2013 01 DE-16-250 10 k (DE-627)1416741267 Neurologische Universitätsklinik 2013 01 DE-16-250 10 s (DE-627)1410501914 Verfasser 2013 01 DE-16-250 10 s pos_7 2013 01 DE-16-250 11 p (DE-627)1515419355 Kurz, Felix T. 2013 01 DE-16-250 11 k (DE-627)1416741267 Neurologische Universitätsklinik 2013 01 DE-16-250 11 k (DE-627)1416466967 Medizinische Fakultät Heidelberg 2013 01 DE-16-250 11 s (DE-627)1410501914 Verfasser 2013 01 DE-16-250 11 s pos_ 8 2013 01 DE-16-250 12 p (DE-627)1547668547 Keßler, Tobias 2013 01 DE-16-250 12 k (DE-627)1416741267 Neurologische Universitätsklinik 2013 01 DE-16-250 12 s (DE-627)1410501914 Verfasser 2013 01 DE-16-250 12 s pos_ 9 2013 01 DE-16-250 13 p (DE-627)1496564405 Heiland, Sabine 2013 01 DE-16-250 13 k (DE-627)1416741267 Neurologische Universitätsklinik 2013 01 DE-16-250 13 s (DE-627)1410501914 Verfasser 2013 01 DE-16-250 13 s pos_ 10 2013 01 DE-16-250 14 p (DE-627)1448137985 Deimling, Andreas von 2013 01 DE-16-250 14 k (DE-627)1416741658 Pathologisches Institut 2013 01 DE-16-250 14 s (DE-627)1410501914 Verfasser 2013 01 DE-16-250 14 s pos_ 11 2013 01 DE-16-250 15 p (DE-627)143607634X Sahm, Felix 2013 01 DE-16-250 15 k (DE-627)1416741658 Pathologisches Institut 2013 01 DE-16-250 15 k (DE-627)1416466967 Medizinische Fakultät Heidelberg 2013 01 DE-16-250 15 s (DE-627)1410501914 Verfasser 2013 01 DE-16-250 15 s pos_ 12 2013 01 DE-16-250 16 p (DE-627)1450189326 Wick, Wolfgang 2013 01 DE-16-250 16 k (DE-627)1416741267 Neurologische Universitätsklinik 2013 01 DE-16-250 16 s (DE-627)1410501914 Verfasser 2013 01 DE-16-250 16 s pos_ 13 2013 01 DE-16-250 17 p (DE-627)1477506500 Winkler, Frank 2013 01 DE-16-250 17 k (DE-627)1416741267 Neurologische Universitätsklinik 2013 01 DE-16-250 17 s (DE-627)1410501914 Verfasser 2013 01 DE-16-250 17 s pos_ 14 |
| allfields_unstemmed |
10.1038/s41467-021-21117-3 doi (DE-627)1755371330 (DE-599)KXP1755371330 (OCoLC)1341405012 DE-627 ger DE-627 rda eng Jung, Erik verfasserin (DE-588)1160204640 (DE-627)1023329875 (DE-576)505549409 aut Tumor cell plasticity, heterogeneity, and resistance in crucial microenvironmental niches in glioma Erik Jung, Matthias Osswald, Miriam Ratliff, Helin Dogan, Ruifan Xie, Sophie Weil, Dirk C. Hoffmann, Felix T. Kurz, Tobias Kessler, Sabine Heiland, Andreas von Deimling, Felix Sahm, Wolfgang Wick and Frank Winkler 12 February 2021 16 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Gesehen am 19.04.2021 Both the perivascular niche (PVN) and the integration into multicellular networks by tumor microtubes (TMs) have been associated with progression and resistance to therapies in glioblastoma, but their specific contribution remained unknown. By long-term tracking of tumor cell fate and dynamics in the live mouse brain, differential therapeutic responses in both niches are determined. Both the PVN, a preferential location of long-term quiescent glioma cells, and network integration facilitate resistance against cytotoxic effects of radiotherapy and chemotherapy—independently of each other, but with additive effects. Perivascular glioblastoma cells are particularly able to actively repair damage to tumor regions. Population of the PVN and resistance in it depend on proficient NOTCH1 expression. In turn, NOTCH1 downregulation induces resistant multicellular networks by TM extension. Our findings identify NOTCH1 as a central switch between the PVN and network niche in glioma, and demonstrate robust cross-compensation when only one niche is targeted. Osswald, Matthias 1982- verfasserin (DE-588)139015620 (DE-627)703181645 (DE-576)309419069 aut Ratliff, Miriam 1979- verfasserin (DE-588)1012081028 (DE-627)660894602 (DE-576)344899357 aut Dogan, Helin 1999- verfasserin (DE-588)1298521866 (DE-627)1854494619 aut Xie, Ruifan verfasserin (DE-588)1153554720 (DE-627)1015049419 (DE-576)500293449 aut Heuer, Sophie 1992- verfasserin (DE-588)1164511882 (DE-627)1028945574 (DE-576)510060609 aut Hoffmann, Dirk C. 1992- verfasserin (DE-588)1231940786 (DE-627)1755605366 aut Kurz, Felix T. 1981- verfasserin (DE-588)1043285474 (DE-627)771321066 (DE-576)394610342 aut Keßler, Tobias 1987- verfasserin (DE-588)1104151693 (DE-627)86164591X (DE-576)470840277 aut Heiland, Sabine verfasserin (DE-588)106732626X (DE-627)818624450 (DE-576)426561368 aut Deimling, Andreas von 1959- verfasserin (DE-588)103034115X (DE-627)735093946 (DE-576)378138065 aut Sahm, Felix 1984- verfasserin (DE-588)1022852132 (DE-627)717318478 (DE-576)366075020 aut Wick, Wolfgang 1970- verfasserin (DE-588)120297736 (DE-627)080586929 (DE-576)186221320 aut Winkler, Frank 1971- verfasserin (DE-588)120794586 (DE-627)704993104 (DE-576)292388586 aut Enthalten in Nature Communications [London] : Springer Nature, 2010 12(2021), Artikel-ID 1014, Seite 1-16 Online-Ressource (DE-627)626457688 (DE-600)2553671-0 (DE-576)331555905 2041-1723 nnns volume:12 year:2021 elocationid:1014 pages:1-16 extent:16 https://doi.org/10.1038/s41467-021-21117-3 Verlag Resolving-System kostenfrei Volltext https://www.nature.com/articles/s41467-021-21117-3 Verlag kostenfrei Volltext GBV_USEFLAG_U GBV_ILN_2011 ISIL_DE-16 SYSFLAG_1 GBV_KXP GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_211 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_2014 GBV_ILN_2110 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4335 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 GBV_ILN_2013 GBV_ILN_2403 GBV_ILN_2013 ISIL_DE-16-250 GBV_ILN_2403 ISIL_DE-LFER AR 12 2021 1014 1-16 16 2011 01 DE-16 4291940599 00 --%%-- --%%-- --%%-- --%%-- l01 17-03-23 2013 01 DE-16-250 3913380442 00 --%%-- --%%-- --%%-- --%%-- l01 19-04-21 2403 01 DE-LFER 4319023765 00 --%%-- --%%-- n --%%-- l01 08-05-23 2403 01 DE-LFER https://doi.org/10.1038/s41467-021-21117-3 2403 01 DE-LFER https://www.nature.com/articles/s41467-021-21117-3 2013 01 DE-16-250 00 s hd2021 2013 01 DE-16-250 01 s (DE-627)1410508463 wissenschaftlicher Artikel (Zeitschrift) 2013 01 DE-16-250 02 s per_14 2013 01 DE-16-250 03 s s_16 2013 01 DE-16-250 04 p (DE-627)1580061443 Jung, Erik 2013 01 DE-16-250 04 k (DE-627)1416741267 Neurologische Universitätsklinik 2013 01 DE-16-250 04 s (DE-627)1410501914 Verfasser 2013 01 DE-16-250 04 s pos_1 2013 01 DE-16-250 05 p (DE-627)1477516328 Osswald, Matthias 2013 01 DE-16-250 05 k (DE-627)1416822720 Extern 2013 01 DE-16-250 05 s (DE-627)1410501914 Verfasser 2013 01 DE-16-250 05 s pos_ 2 2013 01 DE-16-250 06 p (DE-627)1499428073 Ratliff, Miriam 2013 01 DE-16-250 06 k (DE-627)1426595700 Neurochirurgische Klinik 2013 01 DE-16-250 06 s (DE-627)1410501914 Verfasser 2013 01 DE-16-250 06 s pos_3 2013 01 DE-16-250 07 p (DE-627)1854494929 Dogan, Helin 2013 01 DE-16-250 07 k (DE-627)1416466967 Medizinische Fakultät Heidelberg 2013 01 DE-16-250 07 s (DE-627)1410501914 Verfasser 2013 01 DE-16-250 07 s pos_4 2013 01 DE-16-250 08 p (DE-627)1574264605 Xie, Ruifan 2013 01 DE-16-250 08 k (DE-627)1416822720 Extern 2013 01 DE-16-250 08 s (DE-627)1410501914 Verfasser 2013 01 DE-16-250 08 s pos_ 5 2013 01 DE-16-250 09 p (DE-627)1580061478 Heuer, Sophie 2013 01 DE-16-250 09 k (DE-627)1416741267 Neurologische Universitätsklinik 2013 01 DE-16-250 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10.1038/s41467-021-21117-3 doi (DE-627)1755371330 (DE-599)KXP1755371330 (OCoLC)1341405012 DE-627 ger DE-627 rda eng Jung, Erik verfasserin (DE-588)1160204640 (DE-627)1023329875 (DE-576)505549409 aut Tumor cell plasticity, heterogeneity, and resistance in crucial microenvironmental niches in glioma Erik Jung, Matthias Osswald, Miriam Ratliff, Helin Dogan, Ruifan Xie, Sophie Weil, Dirk C. Hoffmann, Felix T. Kurz, Tobias Kessler, Sabine Heiland, Andreas von Deimling, Felix Sahm, Wolfgang Wick and Frank Winkler 12 February 2021 16 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Gesehen am 19.04.2021 Both the perivascular niche (PVN) and the integration into multicellular networks by tumor microtubes (TMs) have been associated with progression and resistance to therapies in glioblastoma, but their specific contribution remained unknown. By long-term tracking of tumor cell fate and dynamics in the live mouse brain, differential therapeutic responses in both niches are determined. Both the PVN, a preferential location of long-term quiescent glioma cells, and network integration facilitate resistance against cytotoxic effects of radiotherapy and chemotherapy—independently of each other, but with additive effects. Perivascular glioblastoma cells are particularly able to actively repair damage to tumor regions. Population of the PVN and resistance in it depend on proficient NOTCH1 expression. In turn, NOTCH1 downregulation induces resistant multicellular networks by TM extension. Our findings identify NOTCH1 as a central switch between the PVN and network niche in glioma, and demonstrate robust cross-compensation when only one niche is targeted. Osswald, Matthias 1982- verfasserin (DE-588)139015620 (DE-627)703181645 (DE-576)309419069 aut Ratliff, Miriam 1979- verfasserin (DE-588)1012081028 (DE-627)660894602 (DE-576)344899357 aut Dogan, Helin 1999- verfasserin (DE-588)1298521866 (DE-627)1854494619 aut Xie, Ruifan verfasserin (DE-588)1153554720 (DE-627)1015049419 (DE-576)500293449 aut Heuer, Sophie 1992- verfasserin (DE-588)1164511882 (DE-627)1028945574 (DE-576)510060609 aut Hoffmann, Dirk C. 1992- verfasserin (DE-588)1231940786 (DE-627)1755605366 aut Kurz, Felix T. 1981- verfasserin (DE-588)1043285474 (DE-627)771321066 (DE-576)394610342 aut Keßler, Tobias 1987- verfasserin (DE-588)1104151693 (DE-627)86164591X (DE-576)470840277 aut Heiland, Sabine verfasserin (DE-588)106732626X (DE-627)818624450 (DE-576)426561368 aut Deimling, Andreas von 1959- verfasserin (DE-588)103034115X (DE-627)735093946 (DE-576)378138065 aut Sahm, Felix 1984- verfasserin (DE-588)1022852132 (DE-627)717318478 (DE-576)366075020 aut Wick, Wolfgang 1970- 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10.1038/s41467-021-21117-3 doi (DE-627)1755371330 (DE-599)KXP1755371330 (OCoLC)1341405012 DE-627 ger DE-627 rda eng Jung, Erik verfasserin (DE-588)1160204640 (DE-627)1023329875 (DE-576)505549409 aut Tumor cell plasticity, heterogeneity, and resistance in crucial microenvironmental niches in glioma Erik Jung, Matthias Osswald, Miriam Ratliff, Helin Dogan, Ruifan Xie, Sophie Weil, Dirk C. Hoffmann, Felix T. Kurz, Tobias Kessler, Sabine Heiland, Andreas von Deimling, Felix Sahm, Wolfgang Wick and Frank Winkler 12 February 2021 16 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Gesehen am 19.04.2021 Both the perivascular niche (PVN) and the integration into multicellular networks by tumor microtubes (TMs) have been associated with progression and resistance to therapies in glioblastoma, but their specific contribution remained unknown. By long-term tracking of tumor cell fate and dynamics in the live mouse brain, differential therapeutic responses in both niches are determined. Both the PVN, a preferential location of long-term quiescent glioma cells, and network integration facilitate resistance against cytotoxic effects of radiotherapy and chemotherapy—independently of each other, but with additive effects. Perivascular glioblastoma cells are particularly able to actively repair damage to tumor regions. Population of the PVN and resistance in it depend on proficient NOTCH1 expression. In turn, NOTCH1 downregulation induces resistant multicellular networks by TM extension. Our findings identify NOTCH1 as a central switch between the PVN and network niche in glioma, and demonstrate robust cross-compensation when only one niche is targeted. 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1755371330 |
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englisch |
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<?xml version="1.0" encoding="UTF-8"?><collection xmlns="http://www.loc.gov/MARC21/slim"><record><leader>01000caa a2200265 4500</leader><controlfield tag="001">1755371330</controlfield><controlfield tag="003">DE-627</controlfield><controlfield tag="005">20231024084318.0</controlfield><controlfield tag="007">cr uuu---uuuuu</controlfield><controlfield tag="008">210419s2021 xx |||||o 00| ||eng c</controlfield><datafield tag="024" ind1="7" ind2=" "><subfield code="a">10.1038/s41467-021-21117-3</subfield><subfield code="2">doi</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(DE-627)1755371330</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(DE-599)KXP1755371330</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(OCoLC)1341405012</subfield></datafield><datafield tag="040" ind1=" " ind2=" "><subfield code="a">DE-627</subfield><subfield code="b">ger</subfield><subfield code="c">DE-627</subfield><subfield code="e">rda</subfield></datafield><datafield tag="041" ind1=" " ind2=" "><subfield code="a">eng</subfield></datafield><datafield tag="100" ind1="1" ind2=" "><subfield code="a">Jung, Erik</subfield><subfield code="e">verfasserin</subfield><subfield code="0">(DE-588)1160204640</subfield><subfield code="0">(DE-627)1023329875</subfield><subfield code="0">(DE-576)505549409</subfield><subfield code="4">aut</subfield></datafield><datafield tag="245" ind1="1" ind2="0"><subfield code="a">Tumor cell plasticity, heterogeneity, and resistance in crucial microenvironmental niches in glioma</subfield><subfield code="c">Erik Jung, Matthias Osswald, Miriam Ratliff, Helin Dogan, Ruifan Xie, Sophie Weil, Dirk C. 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Kurz, Tobias Kessler, Sabine Heiland, Andreas von Deimling, Felix Sahm, Wolfgang Wick and Frank Winkler</subfield></datafield><datafield tag="264" ind1=" " ind2="1"><subfield code="c">12 February 2021</subfield></datafield><datafield tag="300" ind1=" " ind2=" "><subfield code="a">16</subfield></datafield><datafield tag="336" ind1=" " ind2=" "><subfield code="a">Text</subfield><subfield code="b">txt</subfield><subfield code="2">rdacontent</subfield></datafield><datafield tag="337" ind1=" " ind2=" "><subfield code="a">Computermedien</subfield><subfield code="b">c</subfield><subfield code="2">rdamedia</subfield></datafield><datafield tag="338" ind1=" " ind2=" "><subfield code="a">Online-Ressource</subfield><subfield code="b">cr</subfield><subfield code="2">rdacarrier</subfield></datafield><datafield tag="500" ind1=" " ind2=" "><subfield code="a">Gesehen am 19.04.2021</subfield></datafield><datafield tag="520" ind1=" " ind2=" "><subfield code="a">Both the perivascular niche (PVN) and the integration into multicellular networks by tumor microtubes (TMs) have been associated with progression and resistance to therapies in glioblastoma, but their specific contribution remained unknown. 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2013 01 DE-16-250 00 s hd2021 2013 01 DE-16-250 01 s (DE-627)1410508463 wissenschaftlicher Artikel (Zeitschrift) 2013 01 DE-16-250 02 s per_14 2013 01 DE-16-250 03 s s_16 2013 01 DE-16-250 04 p (DE-627)1580061443 Jung, Erik 2013 01 DE-16-250 04 k (DE-627)1416741267 Neurologische Universitätsklinik 2013 01 DE-16-250 04 s (DE-627)1410501914 Verfasser 2013 01 DE-16-250 04 s pos_1 2013 01 DE-16-250 05 p (DE-627)1477516328 Osswald, Matthias 2013 01 DE-16-250 05 k (DE-627)1416822720 Extern 2013 01 DE-16-250 05 s (DE-627)1410501914 Verfasser 2013 01 DE-16-250 05 s pos_ 2 2013 01 DE-16-250 06 p (DE-627)1499428073 Ratliff, Miriam 2013 01 DE-16-250 06 k (DE-627)1426595700 Neurochirurgische Klinik 2013 01 DE-16-250 06 s (DE-627)1410501914 Verfasser 2013 01 DE-16-250 06 s pos_3 2013 01 DE-16-250 07 p (DE-627)1854494929 Dogan, Helin 2013 01 DE-16-250 07 k (DE-627)1416466967 Medizinische Fakultät Heidelberg 2013 01 DE-16-250 07 s (DE-627)1410501914 Verfasser 2013 01 DE-16-250 07 s pos_4 2013 01 DE-16-250 08 p (DE-627)1574264605 Xie, Ruifan 2013 01 DE-16-250 08 k (DE-627)1416822720 Extern 2013 01 DE-16-250 08 s (DE-627)1410501914 Verfasser 2013 01 DE-16-250 08 s pos_ 5 2013 01 DE-16-250 09 p (DE-627)1580061478 Heuer, Sophie 2013 01 DE-16-250 09 k (DE-627)1416741267 Neurologische Universitätsklinik 2013 01 DE-16-250 09 s (DE-627)1410501914 Verfasser 2013 01 DE-16-250 09 s pos_6 2013 01 DE-16-250 10 p (DE-627)1755605471 Hoffmann, Dirk C. 2013 01 DE-16-250 10 k (DE-627)1416741267 Neurologische Universitätsklinik 2013 01 DE-16-250 10 s (DE-627)1410501914 Verfasser 2013 01 DE-16-250 10 s pos_7 2013 01 DE-16-250 11 p (DE-627)1515419355 Kurz, Felix T. 2013 01 DE-16-250 11 k (DE-627)1416741267 Neurologische Universitätsklinik 2013 01 DE-16-250 11 k (DE-627)1416466967 Medizinische Fakultät Heidelberg 2013 01 DE-16-250 11 s (DE-627)1410501914 Verfasser 2013 01 DE-16-250 11 s pos_ 8 2013 01 DE-16-250 12 p (DE-627)1547668547 Keßler, Tobias 2013 01 DE-16-250 12 k (DE-627)1416741267 Neurologische Universitätsklinik 2013 01 DE-16-250 12 s (DE-627)1410501914 Verfasser 2013 01 DE-16-250 12 s pos_ 9 2013 01 DE-16-250 13 p (DE-627)1496564405 Heiland, Sabine 2013 01 DE-16-250 13 k (DE-627)1416741267 Neurologische Universitätsklinik 2013 01 DE-16-250 13 s (DE-627)1410501914 Verfasser 2013 01 DE-16-250 13 s pos_ 10 2013 01 DE-16-250 14 p (DE-627)1448137985 Deimling, Andreas von 2013 01 DE-16-250 14 k (DE-627)1416741658 Pathologisches Institut 2013 01 DE-16-250 14 s (DE-627)1410501914 Verfasser 2013 01 DE-16-250 14 s pos_ 11 2013 01 DE-16-250 15 p (DE-627)143607634X Sahm, Felix 2013 01 DE-16-250 15 k (DE-627)1416741658 Pathologisches Institut 2013 01 DE-16-250 15 k (DE-627)1416466967 Medizinische Fakultät Heidelberg 2013 01 DE-16-250 15 s (DE-627)1410501914 Verfasser 2013 01 DE-16-250 15 s pos_ 12 2013 01 DE-16-250 16 p (DE-627)1450189326 Wick, Wolfgang 2013 01 DE-16-250 16 k (DE-627)1416741267 Neurologische Universitätsklinik 2013 01 DE-16-250 16 s (DE-627)1410501914 Verfasser 2013 01 DE-16-250 16 s pos_ 13 2013 01 DE-16-250 17 p (DE-627)1477506500 Winkler, Frank 2013 01 DE-16-250 17 k (DE-627)1416741267 Neurologische Universitätsklinik 2013 01 DE-16-250 17 s (DE-627)1410501914 Verfasser 2013 01 DE-16-250 17 s pos_ 14 Tumor cell plasticity, heterogeneity, and resistance in crucial microenvironmental niches in glioma Erik Jung, Matthias Osswald, Miriam Ratliff, Helin Dogan, Ruifan Xie, Sophie Weil, Dirk C. Hoffmann, Felix T. Kurz, Tobias Kessler, Sabine Heiland, Andreas von Deimling, Felix Sahm, Wolfgang Wick and Frank Winkler |
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2013 hd2021 2013 wissenschaftlicher Artikel (Zeitschrift) 2013 per_14 2013 s_16 2013 Jung, Erik 2013 Neurologische Universitätsklinik 2013 Verfasser 2013 pos_1 2013 Osswald, Matthias 2013 Extern 2013 pos_ 2 2013 Ratliff, Miriam 2013 Neurochirurgische Klinik 2013 pos_3 2013 Dogan, Helin 2013 Medizinische Fakultät Heidelberg 2013 pos_4 2013 Xie, Ruifan 2013 pos_ 5 2013 Heuer, Sophie 2013 pos_6 2013 Hoffmann, Dirk C. 2013 pos_7 2013 Kurz, Felix T. 2013 pos_ 8 2013 Keßler, Tobias 2013 pos_ 9 2013 Heiland, Sabine 2013 pos_ 10 2013 Deimling, Andreas von 2013 Pathologisches Institut 2013 pos_ 11 2013 Sahm, Felix 2013 pos_ 12 2013 Wick, Wolfgang 2013 pos_ 13 2013 Winkler, Frank 2013 pos_ 14 |
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2013 hd2021 2013 wissenschaftlicher Artikel (Zeitschrift) 2013 per_14 2013 s_16 2013 Jung, Erik 2013 Neurologische Universitätsklinik 2013 Verfasser 2013 pos_1 2013 Osswald, Matthias 2013 Extern 2013 pos_ 2 2013 Ratliff, Miriam 2013 Neurochirurgische Klinik 2013 pos_3 2013 Dogan, Helin 2013 Medizinische Fakultät Heidelberg 2013 pos_4 2013 Xie, Ruifan 2013 pos_ 5 2013 Heuer, Sophie 2013 pos_6 2013 Hoffmann, Dirk C. 2013 pos_7 2013 Kurz, Felix T. 2013 pos_ 8 2013 Keßler, Tobias 2013 pos_ 9 2013 Heiland, Sabine 2013 pos_ 10 2013 Deimling, Andreas von 2013 Pathologisches Institut 2013 pos_ 11 2013 Sahm, Felix 2013 pos_ 12 2013 Wick, Wolfgang 2013 pos_ 13 2013 Winkler, Frank 2013 pos_ 14 |
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Tumor cell plasticity, heterogeneity, and resistance in crucial microenvironmental niches in glioma Erik Jung, Matthias Osswald, Miriam Ratliff, Helin Dogan, Ruifan Xie, Sophie Weil, Dirk C. Hoffmann, Felix T. Kurz, Tobias Kessler, Sabine Heiland, Andreas von Deimling, Felix Sahm, Wolfgang Wick and Frank Winkler |
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tumor cell plasticity, heterogeneity, and resistance in crucial microenvironmental niches in glioma |
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Tumor cell plasticity, heterogeneity, and resistance in crucial microenvironmental niches in glioma |
| abstract |
Both the perivascular niche (PVN) and the integration into multicellular networks by tumor microtubes (TMs) have been associated with progression and resistance to therapies in glioblastoma, but their specific contribution remained unknown. By long-term tracking of tumor cell fate and dynamics in the live mouse brain, differential therapeutic responses in both niches are determined. Both the PVN, a preferential location of long-term quiescent glioma cells, and network integration facilitate resistance against cytotoxic effects of radiotherapy and chemotherapy—independently of each other, but with additive effects. Perivascular glioblastoma cells are particularly able to actively repair damage to tumor regions. Population of the PVN and resistance in it depend on proficient NOTCH1 expression. In turn, NOTCH1 downregulation induces resistant multicellular networks by TM extension. Our findings identify NOTCH1 as a central switch between the PVN and network niche in glioma, and demonstrate robust cross-compensation when only one niche is targeted. Gesehen am 19.04.2021 |
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Both the perivascular niche (PVN) and the integration into multicellular networks by tumor microtubes (TMs) have been associated with progression and resistance to therapies in glioblastoma, but their specific contribution remained unknown. By long-term tracking of tumor cell fate and dynamics in the live mouse brain, differential therapeutic responses in both niches are determined. Both the PVN, a preferential location of long-term quiescent glioma cells, and network integration facilitate resistance against cytotoxic effects of radiotherapy and chemotherapy—independently of each other, but with additive effects. Perivascular glioblastoma cells are particularly able to actively repair damage to tumor regions. Population of the PVN and resistance in it depend on proficient NOTCH1 expression. In turn, NOTCH1 downregulation induces resistant multicellular networks by TM extension. Our findings identify NOTCH1 as a central switch between the PVN and network niche in glioma, and demonstrate robust cross-compensation when only one niche is targeted. Gesehen am 19.04.2021 |
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Both the perivascular niche (PVN) and the integration into multicellular networks by tumor microtubes (TMs) have been associated with progression and resistance to therapies in glioblastoma, but their specific contribution remained unknown. By long-term tracking of tumor cell fate and dynamics in the live mouse brain, differential therapeutic responses in both niches are determined. Both the PVN, a preferential location of long-term quiescent glioma cells, and network integration facilitate resistance against cytotoxic effects of radiotherapy and chemotherapy—independently of each other, but with additive effects. Perivascular glioblastoma cells are particularly able to actively repair damage to tumor regions. Population of the PVN and resistance in it depend on proficient NOTCH1 expression. In turn, NOTCH1 downregulation induces resistant multicellular networks by TM extension. Our findings identify NOTCH1 as a central switch between the PVN and network niche in glioma, and demonstrate robust cross-compensation when only one niche is targeted. Gesehen am 19.04.2021 |
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Tumor cell plasticity, heterogeneity, and resistance in crucial microenvironmental niches in glioma |
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