Spatial Dissection of Invasive Front from Tumor Mass Enables Discovery of Novel microRNA Drivers of Glioblastoma Invasion
Abstract Diffuse invasion is the primary cause of treatment failure of glioblastoma (GBM). Previous studies on GBM invasion have long been forced to use the resected tumor mass cells. Here, a strategy to reliably isolate matching pairs of invasive (GBMINV) and tumor core (GBMTC) cells from the brain...
Ausführliche Beschreibung
Gespeichert in:
| Autor*in: |
Yulun Huang [verfasserIn] Lin Qi [verfasserIn] Mari Kogiso [verfasserIn] Yuchen Du [verfasserIn] Frank K. Braun [verfasserIn] Huiyuan Zhang [verfasserIn] L. Frank Huang [verfasserIn] Sophie Xiao [verfasserIn] Wan‐Yee Teo [verfasserIn] Holly Lindsay [verfasserIn] Sibo Zhao [verfasserIn] Patricia Baxter [verfasserIn] Jack M. F. Su [verfasserIn] Adekunle Adesina [verfasserIn] Jianhua Yang [verfasserIn] Sebastian Brabetz [verfasserIn] Marcel Kool [verfasserIn] Stefan M. Pfister [verfasserIn] Murali Chintagumpala [verfasserIn] Laszlo Perlaky [verfasserIn] Zhong Wang [verfasserIn] Youxin Zhou [verfasserIn] Tsz‐Kwong Man [verfasserIn] Xiao‐Nan Li [verfasserIn] |
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| Format: |
E-Artikel |
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| Sprache: |
Englisch |
| Erschienen: |
2021 |
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| Schlagwörter: |
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| Übergeordnetes Werk: |
In: Advanced Science - Wiley, 2015, 8(2021), 23, Seite n/a-n/a |
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| Übergeordnetes Werk: |
volume:8 ; year:2021 ; number:23 ; pages:n/a-n/a |
| Links: |
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| DOI / URN: |
10.1002/advs.202101923 |
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| Katalog-ID: |
DOAJ052820203 |
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| 245 | 1 | 0 | |a Spatial Dissection of Invasive Front from Tumor Mass Enables Discovery of Novel microRNA Drivers of Glioblastoma Invasion |
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| 520 | |a Abstract Diffuse invasion is the primary cause of treatment failure of glioblastoma (GBM). Previous studies on GBM invasion have long been forced to use the resected tumor mass cells. Here, a strategy to reliably isolate matching pairs of invasive (GBMINV) and tumor core (GBMTC) cells from the brains of 6 highly invasive patient‐derived orthotopic models is described. Direct comparison of these GBMINV and GBMTC cells reveals a significantly elevated invasion capacity in GBMINV cells, detects 23/768 miRNAs over‐expressed in the GBMINV cells (miRNAINV) and 22/768 in the GBMTC cells (miRNATC), respectively. Silencing the top 3 miRNAsINV (miR‐126, miR‐369‐5p, miR‐487b) successfully blocks invasion of GBMINV cells in vitro and in mouse brains. Integrated analysis with mRNA expression identifies miRNAINV target genes and discovers KCNA1 as the sole common computational target gene of which 3 inhibitors significantly suppress invasion in vitro. Furthermore, in vivo treatment with 4‐aminopyridine (4‐AP) effectively eliminates GBM invasion and significantly prolongs animal survival times (P = 0.035). The results highlight the power of spatial dissection of functionally accurate GBMINV and GBMTC cells in identifying novel drivers of GBM invasion and provide strong rationale to support the use of biologically accurate starting materials in understanding cancer invasion and metastasis. | ||
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| 700 | 0 | |a Mari Kogiso |e verfasserin |4 aut | |
| 700 | 0 | |a Yuchen Du |e verfasserin |4 aut | |
| 700 | 0 | |a Frank K. Braun |e verfasserin |4 aut | |
| 700 | 0 | |a Huiyuan Zhang |e verfasserin |4 aut | |
| 700 | 0 | |a L. Frank Huang |e verfasserin |4 aut | |
| 700 | 0 | |a Sophie Xiao |e verfasserin |4 aut | |
| 700 | 0 | |a Wan‐Yee Teo |e verfasserin |4 aut | |
| 700 | 0 | |a Holly Lindsay |e verfasserin |4 aut | |
| 700 | 0 | |a Sibo Zhao |e verfasserin |4 aut | |
| 700 | 0 | |a Patricia Baxter |e verfasserin |4 aut | |
| 700 | 0 | |a Jack M. F. Su |e verfasserin |4 aut | |
| 700 | 0 | |a Adekunle Adesina |e verfasserin |4 aut | |
| 700 | 0 | |a Jianhua Yang |e verfasserin |4 aut | |
| 700 | 0 | |a Sebastian Brabetz |e verfasserin |4 aut | |
| 700 | 0 | |a Marcel Kool |e verfasserin |4 aut | |
| 700 | 0 | |a Stefan M. Pfister |e verfasserin |4 aut | |
| 700 | 0 | |a Murali Chintagumpala |e verfasserin |4 aut | |
| 700 | 0 | |a Laszlo Perlaky |e verfasserin |4 aut | |
| 700 | 0 | |a Zhong Wang |e verfasserin |4 aut | |
| 700 | 0 | |a Youxin Zhou |e verfasserin |4 aut | |
| 700 | 0 | |a Tsz‐Kwong Man |e verfasserin |4 aut | |
| 700 | 0 | |a Xiao‐Nan Li |e verfasserin |4 aut | |
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10.1002/advs.202101923 doi (DE-627)DOAJ052820203 (DE-599)DOAJd951663ff7d440bebd6494e2644f1aa3 DE-627 ger DE-627 rakwb eng Yulun Huang verfasserin aut Spatial Dissection of Invasive Front from Tumor Mass Enables Discovery of Novel microRNA Drivers of Glioblastoma Invasion 2021 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Diffuse invasion is the primary cause of treatment failure of glioblastoma (GBM). Previous studies on GBM invasion have long been forced to use the resected tumor mass cells. Here, a strategy to reliably isolate matching pairs of invasive (GBMINV) and tumor core (GBMTC) cells from the brains of 6 highly invasive patient‐derived orthotopic models is described. Direct comparison of these GBMINV and GBMTC cells reveals a significantly elevated invasion capacity in GBMINV cells, detects 23/768 miRNAs over‐expressed in the GBMINV cells (miRNAINV) and 22/768 in the GBMTC cells (miRNATC), respectively. Silencing the top 3 miRNAsINV (miR‐126, miR‐369‐5p, miR‐487b) successfully blocks invasion of GBMINV cells in vitro and in mouse brains. Integrated analysis with mRNA expression identifies miRNAINV target genes and discovers KCNA1 as the sole common computational target gene of which 3 inhibitors significantly suppress invasion in vitro. Furthermore, in vivo treatment with 4‐aminopyridine (4‐AP) effectively eliminates GBM invasion and significantly prolongs animal survival times (P = 0.035). The results highlight the power of spatial dissection of functionally accurate GBMINV and GBMTC cells in identifying novel drivers of GBM invasion and provide strong rationale to support the use of biologically accurate starting materials in understanding cancer invasion and metastasis. 4‐aminopyridine glioblastoma KCNA1 miRNA patient derived orthotopic xenograft Science Q Lin Qi verfasserin aut Mari Kogiso verfasserin aut Yuchen Du verfasserin aut Frank K. Braun verfasserin aut Huiyuan Zhang verfasserin aut L. Frank Huang verfasserin aut Sophie Xiao verfasserin aut Wan‐Yee Teo verfasserin aut Holly Lindsay verfasserin aut Sibo Zhao verfasserin aut Patricia Baxter verfasserin aut Jack M. F. Su verfasserin aut Adekunle Adesina verfasserin aut Jianhua Yang verfasserin aut Sebastian Brabetz verfasserin aut Marcel Kool verfasserin aut Stefan M. Pfister verfasserin aut Murali Chintagumpala verfasserin aut Laszlo Perlaky verfasserin aut Zhong Wang verfasserin aut Youxin Zhou verfasserin aut Tsz‐Kwong Man verfasserin aut Xiao‐Nan Li verfasserin aut In Advanced Science Wiley, 2015 8(2021), 23, Seite n/a-n/a (DE-627)817357777 (DE-600)2808093-2 21983844 nnns volume:8 year:2021 number:23 pages:n/a-n/a https://doi.org/10.1002/advs.202101923 kostenfrei https://doaj.org/article/d951663ff7d440bebd6494e2644f1aa3 kostenfrei https://doi.org/10.1002/advs.202101923 kostenfrei https://doaj.org/toc/2198-3844 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ 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_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_636 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2106 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2118 GBV_ILN_2122 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2470 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4249 GBV_ILN_4251 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_4326 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 8 2021 23 n/a-n/a |
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10.1002/advs.202101923 doi (DE-627)DOAJ052820203 (DE-599)DOAJd951663ff7d440bebd6494e2644f1aa3 DE-627 ger DE-627 rakwb eng Yulun Huang verfasserin aut Spatial Dissection of Invasive Front from Tumor Mass Enables Discovery of Novel microRNA Drivers of Glioblastoma Invasion 2021 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Diffuse invasion is the primary cause of treatment failure of glioblastoma (GBM). Previous studies on GBM invasion have long been forced to use the resected tumor mass cells. Here, a strategy to reliably isolate matching pairs of invasive (GBMINV) and tumor core (GBMTC) cells from the brains of 6 highly invasive patient‐derived orthotopic models is described. Direct comparison of these GBMINV and GBMTC cells reveals a significantly elevated invasion capacity in GBMINV cells, detects 23/768 miRNAs over‐expressed in the GBMINV cells (miRNAINV) and 22/768 in the GBMTC cells (miRNATC), respectively. Silencing the top 3 miRNAsINV (miR‐126, miR‐369‐5p, miR‐487b) successfully blocks invasion of GBMINV cells in vitro and in mouse brains. Integrated analysis with mRNA expression identifies miRNAINV target genes and discovers KCNA1 as the sole common computational target gene of which 3 inhibitors significantly suppress invasion in vitro. Furthermore, in vivo treatment with 4‐aminopyridine (4‐AP) effectively eliminates GBM invasion and significantly prolongs animal survival times (P = 0.035). The results highlight the power of spatial dissection of functionally accurate GBMINV and GBMTC cells in identifying novel drivers of GBM invasion and provide strong rationale to support the use of biologically accurate starting materials in understanding cancer invasion and metastasis. 4‐aminopyridine glioblastoma KCNA1 miRNA patient derived orthotopic xenograft Science Q Lin Qi verfasserin aut Mari Kogiso verfasserin aut Yuchen Du verfasserin aut Frank K. Braun verfasserin aut Huiyuan Zhang verfasserin aut L. Frank Huang verfasserin aut Sophie Xiao verfasserin aut Wan‐Yee Teo verfasserin aut Holly Lindsay verfasserin aut Sibo Zhao verfasserin aut Patricia Baxter verfasserin aut Jack M. F. Su verfasserin aut Adekunle Adesina verfasserin aut Jianhua Yang verfasserin aut Sebastian Brabetz verfasserin aut Marcel Kool verfasserin aut Stefan M. Pfister verfasserin aut Murali Chintagumpala verfasserin aut Laszlo Perlaky verfasserin aut Zhong Wang verfasserin aut Youxin Zhou verfasserin aut Tsz‐Kwong Man verfasserin aut Xiao‐Nan Li verfasserin aut In Advanced Science Wiley, 2015 8(2021), 23, Seite n/a-n/a (DE-627)817357777 (DE-600)2808093-2 21983844 nnns volume:8 year:2021 number:23 pages:n/a-n/a https://doi.org/10.1002/advs.202101923 kostenfrei https://doaj.org/article/d951663ff7d440bebd6494e2644f1aa3 kostenfrei https://doi.org/10.1002/advs.202101923 kostenfrei https://doaj.org/toc/2198-3844 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ 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_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_636 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2106 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2118 GBV_ILN_2122 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2470 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4249 GBV_ILN_4251 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_4326 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 8 2021 23 n/a-n/a |
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10.1002/advs.202101923 doi (DE-627)DOAJ052820203 (DE-599)DOAJd951663ff7d440bebd6494e2644f1aa3 DE-627 ger DE-627 rakwb eng Yulun Huang verfasserin aut Spatial Dissection of Invasive Front from Tumor Mass Enables Discovery of Novel microRNA Drivers of Glioblastoma Invasion 2021 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Diffuse invasion is the primary cause of treatment failure of glioblastoma (GBM). Previous studies on GBM invasion have long been forced to use the resected tumor mass cells. Here, a strategy to reliably isolate matching pairs of invasive (GBMINV) and tumor core (GBMTC) cells from the brains of 6 highly invasive patient‐derived orthotopic models is described. Direct comparison of these GBMINV and GBMTC cells reveals a significantly elevated invasion capacity in GBMINV cells, detects 23/768 miRNAs over‐expressed in the GBMINV cells (miRNAINV) and 22/768 in the GBMTC cells (miRNATC), respectively. Silencing the top 3 miRNAsINV (miR‐126, miR‐369‐5p, miR‐487b) successfully blocks invasion of GBMINV cells in vitro and in mouse brains. Integrated analysis with mRNA expression identifies miRNAINV target genes and discovers KCNA1 as the sole common computational target gene of which 3 inhibitors significantly suppress invasion in vitro. Furthermore, in vivo treatment with 4‐aminopyridine (4‐AP) effectively eliminates GBM invasion and significantly prolongs animal survival times (P = 0.035). The results highlight the power of spatial dissection of functionally accurate GBMINV and GBMTC cells in identifying novel drivers of GBM invasion and provide strong rationale to support the use of biologically accurate starting materials in understanding cancer invasion and metastasis. 4‐aminopyridine glioblastoma KCNA1 miRNA patient derived orthotopic xenograft Science Q Lin Qi verfasserin aut Mari Kogiso verfasserin aut Yuchen Du verfasserin aut Frank K. Braun verfasserin aut Huiyuan Zhang verfasserin aut L. Frank Huang verfasserin aut Sophie Xiao verfasserin aut Wan‐Yee Teo verfasserin aut Holly Lindsay verfasserin aut Sibo Zhao verfasserin aut Patricia Baxter verfasserin aut Jack M. F. Su verfasserin aut Adekunle Adesina verfasserin aut Jianhua Yang verfasserin aut Sebastian Brabetz verfasserin aut Marcel Kool verfasserin aut Stefan M. Pfister verfasserin aut Murali Chintagumpala verfasserin aut Laszlo Perlaky verfasserin aut Zhong Wang verfasserin aut Youxin Zhou verfasserin aut Tsz‐Kwong Man verfasserin aut Xiao‐Nan Li verfasserin aut In Advanced Science Wiley, 2015 8(2021), 23, Seite n/a-n/a (DE-627)817357777 (DE-600)2808093-2 21983844 nnns volume:8 year:2021 number:23 pages:n/a-n/a https://doi.org/10.1002/advs.202101923 kostenfrei https://doaj.org/article/d951663ff7d440bebd6494e2644f1aa3 kostenfrei https://doi.org/10.1002/advs.202101923 kostenfrei https://doaj.org/toc/2198-3844 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ 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_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_636 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2106 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2118 GBV_ILN_2122 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2470 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4249 GBV_ILN_4251 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_4326 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 8 2021 23 n/a-n/a |
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10.1002/advs.202101923 doi (DE-627)DOAJ052820203 (DE-599)DOAJd951663ff7d440bebd6494e2644f1aa3 DE-627 ger DE-627 rakwb eng Yulun Huang verfasserin aut Spatial Dissection of Invasive Front from Tumor Mass Enables Discovery of Novel microRNA Drivers of Glioblastoma Invasion 2021 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Diffuse invasion is the primary cause of treatment failure of glioblastoma (GBM). Previous studies on GBM invasion have long been forced to use the resected tumor mass cells. Here, a strategy to reliably isolate matching pairs of invasive (GBMINV) and tumor core (GBMTC) cells from the brains of 6 highly invasive patient‐derived orthotopic models is described. Direct comparison of these GBMINV and GBMTC cells reveals a significantly elevated invasion capacity in GBMINV cells, detects 23/768 miRNAs over‐expressed in the GBMINV cells (miRNAINV) and 22/768 in the GBMTC cells (miRNATC), respectively. Silencing the top 3 miRNAsINV (miR‐126, miR‐369‐5p, miR‐487b) successfully blocks invasion of GBMINV cells in vitro and in mouse brains. Integrated analysis with mRNA expression identifies miRNAINV target genes and discovers KCNA1 as the sole common computational target gene of which 3 inhibitors significantly suppress invasion in vitro. Furthermore, in vivo treatment with 4‐aminopyridine (4‐AP) effectively eliminates GBM invasion and significantly prolongs animal survival times (P = 0.035). The results highlight the power of spatial dissection of functionally accurate GBMINV and GBMTC cells in identifying novel drivers of GBM invasion and provide strong rationale to support the use of biologically accurate starting materials in understanding cancer invasion and metastasis. 4‐aminopyridine glioblastoma KCNA1 miRNA patient derived orthotopic xenograft Science Q Lin Qi verfasserin aut Mari Kogiso verfasserin aut Yuchen Du verfasserin aut Frank K. Braun verfasserin aut Huiyuan Zhang verfasserin aut L. Frank Huang verfasserin aut Sophie Xiao verfasserin aut Wan‐Yee Teo verfasserin aut Holly Lindsay verfasserin aut Sibo Zhao verfasserin aut Patricia Baxter verfasserin aut Jack M. F. Su verfasserin aut Adekunle Adesina verfasserin aut Jianhua Yang verfasserin aut Sebastian Brabetz verfasserin aut Marcel Kool verfasserin aut Stefan M. Pfister verfasserin aut Murali Chintagumpala verfasserin aut Laszlo Perlaky verfasserin aut Zhong Wang verfasserin aut Youxin Zhou verfasserin aut Tsz‐Kwong Man verfasserin aut Xiao‐Nan Li verfasserin aut In Advanced Science Wiley, 2015 8(2021), 23, Seite n/a-n/a (DE-627)817357777 (DE-600)2808093-2 21983844 nnns volume:8 year:2021 number:23 pages:n/a-n/a https://doi.org/10.1002/advs.202101923 kostenfrei https://doaj.org/article/d951663ff7d440bebd6494e2644f1aa3 kostenfrei https://doi.org/10.1002/advs.202101923 kostenfrei https://doaj.org/toc/2198-3844 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ 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_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_636 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2106 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2118 GBV_ILN_2122 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2470 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4249 GBV_ILN_4251 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_4326 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 8 2021 23 n/a-n/a |
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10.1002/advs.202101923 doi (DE-627)DOAJ052820203 (DE-599)DOAJd951663ff7d440bebd6494e2644f1aa3 DE-627 ger DE-627 rakwb eng Yulun Huang verfasserin aut Spatial Dissection of Invasive Front from Tumor Mass Enables Discovery of Novel microRNA Drivers of Glioblastoma Invasion 2021 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Diffuse invasion is the primary cause of treatment failure of glioblastoma (GBM). Previous studies on GBM invasion have long been forced to use the resected tumor mass cells. Here, a strategy to reliably isolate matching pairs of invasive (GBMINV) and tumor core (GBMTC) cells from the brains of 6 highly invasive patient‐derived orthotopic models is described. Direct comparison of these GBMINV and GBMTC cells reveals a significantly elevated invasion capacity in GBMINV cells, detects 23/768 miRNAs over‐expressed in the GBMINV cells (miRNAINV) and 22/768 in the GBMTC cells (miRNATC), respectively. Silencing the top 3 miRNAsINV (miR‐126, miR‐369‐5p, miR‐487b) successfully blocks invasion of GBMINV cells in vitro and in mouse brains. Integrated analysis with mRNA expression identifies miRNAINV target genes and discovers KCNA1 as the sole common computational target gene of which 3 inhibitors significantly suppress invasion in vitro. Furthermore, in vivo treatment with 4‐aminopyridine (4‐AP) effectively eliminates GBM invasion and significantly prolongs animal survival times (P = 0.035). The results highlight the power of spatial dissection of functionally accurate GBMINV and GBMTC cells in identifying novel drivers of GBM invasion and provide strong rationale to support the use of biologically accurate starting materials in understanding cancer invasion and metastasis. 4‐aminopyridine glioblastoma KCNA1 miRNA patient derived orthotopic xenograft Science Q Lin Qi verfasserin aut Mari Kogiso verfasserin aut Yuchen Du verfasserin aut Frank K. Braun verfasserin aut Huiyuan Zhang verfasserin aut L. Frank Huang verfasserin aut Sophie Xiao verfasserin aut Wan‐Yee Teo verfasserin aut Holly Lindsay verfasserin aut Sibo Zhao verfasserin aut Patricia Baxter verfasserin aut Jack M. F. Su verfasserin aut Adekunle Adesina verfasserin aut Jianhua Yang verfasserin aut Sebastian Brabetz verfasserin aut Marcel Kool verfasserin aut Stefan M. Pfister verfasserin aut Murali Chintagumpala verfasserin aut Laszlo Perlaky verfasserin aut Zhong Wang verfasserin aut Youxin Zhou verfasserin aut Tsz‐Kwong Man verfasserin aut Xiao‐Nan Li verfasserin aut In Advanced Science Wiley, 2015 8(2021), 23, Seite n/a-n/a (DE-627)817357777 (DE-600)2808093-2 21983844 nnns volume:8 year:2021 number:23 pages:n/a-n/a https://doi.org/10.1002/advs.202101923 kostenfrei https://doaj.org/article/d951663ff7d440bebd6494e2644f1aa3 kostenfrei https://doi.org/10.1002/advs.202101923 kostenfrei https://doaj.org/toc/2198-3844 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ 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_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_636 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2106 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2118 GBV_ILN_2122 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2470 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4249 GBV_ILN_4251 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_4326 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 8 2021 23 n/a-n/a |
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Yulun Huang @@aut@@ Lin Qi @@aut@@ Mari Kogiso @@aut@@ Yuchen Du @@aut@@ Frank K. Braun @@aut@@ Huiyuan Zhang @@aut@@ L. Frank Huang @@aut@@ Sophie Xiao @@aut@@ Wan‐Yee Teo @@aut@@ Holly Lindsay @@aut@@ Sibo Zhao @@aut@@ Patricia Baxter @@aut@@ Jack M. F. Su @@aut@@ Adekunle Adesina @@aut@@ Jianhua Yang @@aut@@ Sebastian Brabetz @@aut@@ Marcel Kool @@aut@@ Stefan M. Pfister @@aut@@ Murali Chintagumpala @@aut@@ Laszlo Perlaky @@aut@@ Zhong Wang @@aut@@ Youxin Zhou @@aut@@ Tsz‐Kwong Man @@aut@@ Xiao‐Nan Li @@aut@@ |
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Previous studies on GBM invasion have long been forced to use the resected tumor mass cells. Here, a strategy to reliably isolate matching pairs of invasive (GBMINV) and tumor core (GBMTC) cells from the brains of 6 highly invasive patient‐derived orthotopic models is described. Direct comparison of these GBMINV and GBMTC cells reveals a significantly elevated invasion capacity in GBMINV cells, detects 23/768 miRNAs over‐expressed in the GBMINV cells (miRNAINV) and 22/768 in the GBMTC cells (miRNATC), respectively. Silencing the top 3 miRNAsINV (miR‐126, miR‐369‐5p, miR‐487b) successfully blocks invasion of GBMINV cells in vitro and in mouse brains. Integrated analysis with mRNA expression identifies miRNAINV target genes and discovers KCNA1 as the sole common computational target gene of which 3 inhibitors significantly suppress invasion in vitro. 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Yulun Huang |
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Yulun Huang misc 4‐aminopyridine misc glioblastoma misc KCNA1 misc miRNA misc patient derived orthotopic xenograft misc Science misc Q Spatial Dissection of Invasive Front from Tumor Mass Enables Discovery of Novel microRNA Drivers of Glioblastoma Invasion |
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Spatial Dissection of Invasive Front from Tumor Mass Enables Discovery of Novel microRNA Drivers of Glioblastoma Invasion 4‐aminopyridine glioblastoma KCNA1 miRNA patient derived orthotopic xenograft |
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Spatial Dissection of Invasive Front from Tumor Mass Enables Discovery of Novel microRNA Drivers of Glioblastoma Invasion |
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Yulun Huang Lin Qi Mari Kogiso Yuchen Du Frank K. Braun Huiyuan Zhang L. Frank Huang Sophie Xiao Wan‐Yee Teo Holly Lindsay Sibo Zhao Patricia Baxter Jack M. F. Su Adekunle Adesina Jianhua Yang Sebastian Brabetz Marcel Kool Stefan M. Pfister Murali Chintagumpala Laszlo Perlaky Zhong Wang Youxin Zhou Tsz‐Kwong Man Xiao‐Nan Li |
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spatial dissection of invasive front from tumor mass enables discovery of novel microrna drivers of glioblastoma invasion |
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Spatial Dissection of Invasive Front from Tumor Mass Enables Discovery of Novel microRNA Drivers of Glioblastoma Invasion |
| abstract |
Abstract Diffuse invasion is the primary cause of treatment failure of glioblastoma (GBM). Previous studies on GBM invasion have long been forced to use the resected tumor mass cells. Here, a strategy to reliably isolate matching pairs of invasive (GBMINV) and tumor core (GBMTC) cells from the brains of 6 highly invasive patient‐derived orthotopic models is described. Direct comparison of these GBMINV and GBMTC cells reveals a significantly elevated invasion capacity in GBMINV cells, detects 23/768 miRNAs over‐expressed in the GBMINV cells (miRNAINV) and 22/768 in the GBMTC cells (miRNATC), respectively. Silencing the top 3 miRNAsINV (miR‐126, miR‐369‐5p, miR‐487b) successfully blocks invasion of GBMINV cells in vitro and in mouse brains. Integrated analysis with mRNA expression identifies miRNAINV target genes and discovers KCNA1 as the sole common computational target gene of which 3 inhibitors significantly suppress invasion in vitro. Furthermore, in vivo treatment with 4‐aminopyridine (4‐AP) effectively eliminates GBM invasion and significantly prolongs animal survival times (P = 0.035). The results highlight the power of spatial dissection of functionally accurate GBMINV and GBMTC cells in identifying novel drivers of GBM invasion and provide strong rationale to support the use of biologically accurate starting materials in understanding cancer invasion and metastasis. |
| abstractGer |
Abstract Diffuse invasion is the primary cause of treatment failure of glioblastoma (GBM). Previous studies on GBM invasion have long been forced to use the resected tumor mass cells. Here, a strategy to reliably isolate matching pairs of invasive (GBMINV) and tumor core (GBMTC) cells from the brains of 6 highly invasive patient‐derived orthotopic models is described. Direct comparison of these GBMINV and GBMTC cells reveals a significantly elevated invasion capacity in GBMINV cells, detects 23/768 miRNAs over‐expressed in the GBMINV cells (miRNAINV) and 22/768 in the GBMTC cells (miRNATC), respectively. Silencing the top 3 miRNAsINV (miR‐126, miR‐369‐5p, miR‐487b) successfully blocks invasion of GBMINV cells in vitro and in mouse brains. Integrated analysis with mRNA expression identifies miRNAINV target genes and discovers KCNA1 as the sole common computational target gene of which 3 inhibitors significantly suppress invasion in vitro. Furthermore, in vivo treatment with 4‐aminopyridine (4‐AP) effectively eliminates GBM invasion and significantly prolongs animal survival times (P = 0.035). The results highlight the power of spatial dissection of functionally accurate GBMINV and GBMTC cells in identifying novel drivers of GBM invasion and provide strong rationale to support the use of biologically accurate starting materials in understanding cancer invasion and metastasis. |
| abstract_unstemmed |
Abstract Diffuse invasion is the primary cause of treatment failure of glioblastoma (GBM). Previous studies on GBM invasion have long been forced to use the resected tumor mass cells. Here, a strategy to reliably isolate matching pairs of invasive (GBMINV) and tumor core (GBMTC) cells from the brains of 6 highly invasive patient‐derived orthotopic models is described. Direct comparison of these GBMINV and GBMTC cells reveals a significantly elevated invasion capacity in GBMINV cells, detects 23/768 miRNAs over‐expressed in the GBMINV cells (miRNAINV) and 22/768 in the GBMTC cells (miRNATC), respectively. Silencing the top 3 miRNAsINV (miR‐126, miR‐369‐5p, miR‐487b) successfully blocks invasion of GBMINV cells in vitro and in mouse brains. Integrated analysis with mRNA expression identifies miRNAINV target genes and discovers KCNA1 as the sole common computational target gene of which 3 inhibitors significantly suppress invasion in vitro. Furthermore, in vivo treatment with 4‐aminopyridine (4‐AP) effectively eliminates GBM invasion and significantly prolongs animal survival times (P = 0.035). The results highlight the power of spatial dissection of functionally accurate GBMINV and GBMTC cells in identifying novel drivers of GBM invasion and provide strong rationale to support the use of biologically accurate starting materials in understanding cancer invasion and metastasis. |
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Spatial Dissection of Invasive Front from Tumor Mass Enables Discovery of Novel microRNA Drivers of Glioblastoma Invasion |
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Lin Qi Mari Kogiso Yuchen Du Frank K. Braun Huiyuan Zhang L. Frank Huang Sophie Xiao Wan‐Yee Teo Holly Lindsay Sibo Zhao Patricia Baxter Jack M. F. Su Adekunle Adesina Jianhua Yang Sebastian Brabetz Marcel Kool Stefan M. Pfister Murali Chintagumpala Laszlo Perlaky Zhong Wang Youxin Zhou Tsz‐Kwong Man Xiao‐Nan Li |
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|
| score |
7.40199 |