Fibroblasts in Nodular Sclerosing Classical Hodgkin Lymphoma Are Defined by a Specific Phenotype and Protect Tumor Cells from Brentuximab-Vedotin Induced Injury

Classical Hodgkin lymphoma (cHL) is one of the most common malignant lymphomas in Western Europe. The nodular sclerosing subtype of cHL (NS cHL) is characterized by a proliferation of fibroblasts in the tumor microenvironment, leading to fibrotic bands surrounding the lymphoma infiltrate. Several st...
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Autor*in:	Katrin Bankov [verfasserIn] Claudia Döring [verfasserIn] Adam Ustaszewski [verfasserIn] Maciej Giefing [verfasserIn] Marco Herling [verfasserIn] Chiara Cencioni [verfasserIn] Francesco Spallotta [verfasserIn] Carlo Gaetano [verfasserIn] Ralf Küppers [verfasserIn] Martin-Leo Hansmann [verfasserIn] Sylvia Hartmann [verfasserIn]

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2019

Schlagwörter:	classical hodgkin lymphoma nodular sclerosis fibroblasts gene expression analysis methylation profiling luteolin

Übergeordnetes Werk:	In: Cancers - MDPI AG, 2010, 11(2019), 11, p 1687
Übergeordnetes Werk:	volume:11 ; year:2019 ; number:11, p 1687

Links:	Link aufrufen Link aufrufen Link aufrufen Journal toc

DOI / URN:	10.3390/cancers11111687

Katalog-ID:	DOAJ060760087

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520			\|a Classical Hodgkin lymphoma (cHL) is one of the most common malignant lymphomas in Western Europe. The nodular sclerosing subtype of cHL (NS cHL) is characterized by a proliferation of fibroblasts in the tumor microenvironment, leading to fibrotic bands surrounding the lymphoma infiltrate. Several studies have described a crosstalk between the tumour cells of cHL, the Hodgkin- and Reed-Sternberg (HRS) cells, and cancer-associated fibroblasts. However, to date a deep molecular characterization of these fibroblasts is lacking. Thus, the aim of the present study is a comprehensive characterization of these fibroblasts. Gene expression profiling and methylation profiles of fibroblasts isolated from primary lymph node suspensions revealed persistent differences between fibroblasts obtained from NS cHL and lymphadenitis. NS cHL derived fibroblasts exhibit a myofibroblastic phenotype characterized by myocardin (<i<MYOCD</i<) expression. Moreover, <i<TIMP3</i<, an inhibitor of matrix metalloproteinases, was strongly upregulated in NS cHL fibroblasts, likely contributing to the accumulation of collagen in sclerotic bands of NS cHL. As previously shown for other types of cancer-associated fibroblasts, treatment by luteolin could reverse this fibroblast phenotype and decrease TIMP3 secretion. NS cHL fibroblasts showed enhanced proliferation when they were exposed to soluble factors released from HRS cells. For HRS cells, soluble factors from fibroblasts were not sufficient to protect them from Brentuximab-Vedotin induced cell death. However, HRS cells adherent to fibroblasts were protected from Brentuximab-Vedotin induced injury. In summary, we confirm the importance of fibroblasts for HRS cell survival and identify TIMP3 which probably contributes as a major factor to the typical fibrosis observed in NS cHL.
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653		0	\|a Neoplasms. Tumors. Oncology. Including cancer and carcinogens
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allfields	10.3390/cancers11111687 doi (DE-627)DOAJ060760087 (DE-599)DOAJ7f45eeec31804da08a3fa2d86ed999b5 DE-627 ger DE-627 rakwb eng RC254-282 Katrin Bankov verfasserin aut Fibroblasts in Nodular Sclerosing Classical Hodgkin Lymphoma Are Defined by a Specific Phenotype and Protect Tumor Cells from Brentuximab-Vedotin Induced Injury 2019 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Classical Hodgkin lymphoma (cHL) is one of the most common malignant lymphomas in Western Europe. The nodular sclerosing subtype of cHL (NS cHL) is characterized by a proliferation of fibroblasts in the tumor microenvironment, leading to fibrotic bands surrounding the lymphoma infiltrate. Several studies have described a crosstalk between the tumour cells of cHL, the Hodgkin- and Reed-Sternberg (HRS) cells, and cancer-associated fibroblasts. However, to date a deep molecular characterization of these fibroblasts is lacking. Thus, the aim of the present study is a comprehensive characterization of these fibroblasts. Gene expression profiling and methylation profiles of fibroblasts isolated from primary lymph node suspensions revealed persistent differences between fibroblasts obtained from NS cHL and lymphadenitis. NS cHL derived fibroblasts exhibit a myofibroblastic phenotype characterized by myocardin (<i<MYOCD</i<) expression. Moreover, <i<TIMP3</i<, an inhibitor of matrix metalloproteinases, was strongly upregulated in NS cHL fibroblasts, likely contributing to the accumulation of collagen in sclerotic bands of NS cHL. As previously shown for other types of cancer-associated fibroblasts, treatment by luteolin could reverse this fibroblast phenotype and decrease TIMP3 secretion. NS cHL fibroblasts showed enhanced proliferation when they were exposed to soluble factors released from HRS cells. For HRS cells, soluble factors from fibroblasts were not sufficient to protect them from Brentuximab-Vedotin induced cell death. However, HRS cells adherent to fibroblasts were protected from Brentuximab-Vedotin induced injury. In summary, we confirm the importance of fibroblasts for HRS cell survival and identify TIMP3 which probably contributes as a major factor to the typical fibrosis observed in NS cHL. classical hodgkin lymphoma nodular sclerosis fibroblasts gene expression analysis methylation profiling luteolin Neoplasms. Tumors. Oncology. Including cancer and carcinogens Claudia Döring verfasserin aut Adam Ustaszewski verfasserin aut Maciej Giefing verfasserin aut Marco Herling verfasserin aut Chiara Cencioni verfasserin aut Francesco Spallotta verfasserin aut Carlo Gaetano verfasserin aut Ralf Küppers verfasserin aut Martin-Leo Hansmann verfasserin aut Sylvia Hartmann verfasserin aut In Cancers MDPI AG, 2010 11(2019), 11, p 1687 (DE-627)614095670 (DE-600)2527080-1 20726694 nnns volume:11 year:2019 number:11, p 1687 https://doi.org/10.3390/cancers11111687 kostenfrei https://doaj.org/article/7f45eeec31804da08a3fa2d86ed999b5 kostenfrei https://www.mdpi.com/2072-6694/11/11/1687 kostenfrei https://doaj.org/toc/2072-6694 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 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_4338 GBV_ILN_4367 GBV_ILN_4700 AR 11 2019 11, p 1687
spelling	10.3390/cancers11111687 doi (DE-627)DOAJ060760087 (DE-599)DOAJ7f45eeec31804da08a3fa2d86ed999b5 DE-627 ger DE-627 rakwb eng RC254-282 Katrin Bankov verfasserin aut Fibroblasts in Nodular Sclerosing Classical Hodgkin Lymphoma Are Defined by a Specific Phenotype and Protect Tumor Cells from Brentuximab-Vedotin Induced Injury 2019 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Classical Hodgkin lymphoma (cHL) is one of the most common malignant lymphomas in Western Europe. The nodular sclerosing subtype of cHL (NS cHL) is characterized by a proliferation of fibroblasts in the tumor microenvironment, leading to fibrotic bands surrounding the lymphoma infiltrate. Several studies have described a crosstalk between the tumour cells of cHL, the Hodgkin- and Reed-Sternberg (HRS) cells, and cancer-associated fibroblasts. However, to date a deep molecular characterization of these fibroblasts is lacking. Thus, the aim of the present study is a comprehensive characterization of these fibroblasts. Gene expression profiling and methylation profiles of fibroblasts isolated from primary lymph node suspensions revealed persistent differences between fibroblasts obtained from NS cHL and lymphadenitis. NS cHL derived fibroblasts exhibit a myofibroblastic phenotype characterized by myocardin (<i<MYOCD</i<) expression. Moreover, <i<TIMP3</i<, an inhibitor of matrix metalloproteinases, was strongly upregulated in NS cHL fibroblasts, likely contributing to the accumulation of collagen in sclerotic bands of NS cHL. As previously shown for other types of cancer-associated fibroblasts, treatment by luteolin could reverse this fibroblast phenotype and decrease TIMP3 secretion. NS cHL fibroblasts showed enhanced proliferation when they were exposed to soluble factors released from HRS cells. For HRS cells, soluble factors from fibroblasts were not sufficient to protect them from Brentuximab-Vedotin induced cell death. However, HRS cells adherent to fibroblasts were protected from Brentuximab-Vedotin induced injury. In summary, we confirm the importance of fibroblasts for HRS cell survival and identify TIMP3 which probably contributes as a major factor to the typical fibrosis observed in NS cHL. classical hodgkin lymphoma nodular sclerosis fibroblasts gene expression analysis methylation profiling luteolin Neoplasms. Tumors. Oncology. Including cancer and carcinogens Claudia Döring verfasserin aut Adam Ustaszewski verfasserin aut Maciej Giefing verfasserin aut Marco Herling verfasserin aut Chiara Cencioni verfasserin aut Francesco Spallotta verfasserin aut Carlo Gaetano verfasserin aut Ralf Küppers verfasserin aut Martin-Leo Hansmann verfasserin aut Sylvia Hartmann verfasserin aut In Cancers MDPI AG, 2010 11(2019), 11, p 1687 (DE-627)614095670 (DE-600)2527080-1 20726694 nnns volume:11 year:2019 number:11, p 1687 https://doi.org/10.3390/cancers11111687 kostenfrei https://doaj.org/article/7f45eeec31804da08a3fa2d86ed999b5 kostenfrei https://www.mdpi.com/2072-6694/11/11/1687 kostenfrei https://doaj.org/toc/2072-6694 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 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_4338 GBV_ILN_4367 GBV_ILN_4700 AR 11 2019 11, p 1687
allfields_unstemmed	10.3390/cancers11111687 doi (DE-627)DOAJ060760087 (DE-599)DOAJ7f45eeec31804da08a3fa2d86ed999b5 DE-627 ger DE-627 rakwb eng RC254-282 Katrin Bankov verfasserin aut Fibroblasts in Nodular Sclerosing Classical Hodgkin Lymphoma Are Defined by a Specific Phenotype and Protect Tumor Cells from Brentuximab-Vedotin Induced Injury 2019 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Classical Hodgkin lymphoma (cHL) is one of the most common malignant lymphomas in Western Europe. The nodular sclerosing subtype of cHL (NS cHL) is characterized by a proliferation of fibroblasts in the tumor microenvironment, leading to fibrotic bands surrounding the lymphoma infiltrate. Several studies have described a crosstalk between the tumour cells of cHL, the Hodgkin- and Reed-Sternberg (HRS) cells, and cancer-associated fibroblasts. However, to date a deep molecular characterization of these fibroblasts is lacking. Thus, the aim of the present study is a comprehensive characterization of these fibroblasts. Gene expression profiling and methylation profiles of fibroblasts isolated from primary lymph node suspensions revealed persistent differences between fibroblasts obtained from NS cHL and lymphadenitis. NS cHL derived fibroblasts exhibit a myofibroblastic phenotype characterized by myocardin (<i<MYOCD</i<) expression. Moreover, <i<TIMP3</i<, an inhibitor of matrix metalloproteinases, was strongly upregulated in NS cHL fibroblasts, likely contributing to the accumulation of collagen in sclerotic bands of NS cHL. As previously shown for other types of cancer-associated fibroblasts, treatment by luteolin could reverse this fibroblast phenotype and decrease TIMP3 secretion. NS cHL fibroblasts showed enhanced proliferation when they were exposed to soluble factors released from HRS cells. For HRS cells, soluble factors from fibroblasts were not sufficient to protect them from Brentuximab-Vedotin induced cell death. However, HRS cells adherent to fibroblasts were protected from Brentuximab-Vedotin induced injury. In summary, we confirm the importance of fibroblasts for HRS cell survival and identify TIMP3 which probably contributes as a major factor to the typical fibrosis observed in NS cHL. classical hodgkin lymphoma nodular sclerosis fibroblasts gene expression analysis methylation profiling luteolin Neoplasms. Tumors. Oncology. Including cancer and carcinogens Claudia Döring verfasserin aut Adam Ustaszewski verfasserin aut Maciej Giefing verfasserin aut Marco Herling verfasserin aut Chiara Cencioni verfasserin aut Francesco Spallotta verfasserin aut Carlo Gaetano verfasserin aut Ralf Küppers verfasserin aut Martin-Leo Hansmann verfasserin aut Sylvia Hartmann verfasserin aut In Cancers MDPI AG, 2010 11(2019), 11, p 1687 (DE-627)614095670 (DE-600)2527080-1 20726694 nnns volume:11 year:2019 number:11, p 1687 https://doi.org/10.3390/cancers11111687 kostenfrei https://doaj.org/article/7f45eeec31804da08a3fa2d86ed999b5 kostenfrei https://www.mdpi.com/2072-6694/11/11/1687 kostenfrei https://doaj.org/toc/2072-6694 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 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_4338 GBV_ILN_4367 GBV_ILN_4700 AR 11 2019 11, p 1687
allfieldsGer	10.3390/cancers11111687 doi (DE-627)DOAJ060760087 (DE-599)DOAJ7f45eeec31804da08a3fa2d86ed999b5 DE-627 ger DE-627 rakwb eng RC254-282 Katrin Bankov verfasserin aut Fibroblasts in Nodular Sclerosing Classical Hodgkin Lymphoma Are Defined by a Specific Phenotype and Protect Tumor Cells from Brentuximab-Vedotin Induced Injury 2019 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Classical Hodgkin lymphoma (cHL) is one of the most common malignant lymphomas in Western Europe. The nodular sclerosing subtype of cHL (NS cHL) is characterized by a proliferation of fibroblasts in the tumor microenvironment, leading to fibrotic bands surrounding the lymphoma infiltrate. Several studies have described a crosstalk between the tumour cells of cHL, the Hodgkin- and Reed-Sternberg (HRS) cells, and cancer-associated fibroblasts. However, to date a deep molecular characterization of these fibroblasts is lacking. Thus, the aim of the present study is a comprehensive characterization of these fibroblasts. Gene expression profiling and methylation profiles of fibroblasts isolated from primary lymph node suspensions revealed persistent differences between fibroblasts obtained from NS cHL and lymphadenitis. NS cHL derived fibroblasts exhibit a myofibroblastic phenotype characterized by myocardin (<i<MYOCD</i<) expression. Moreover, <i<TIMP3</i<, an inhibitor of matrix metalloproteinases, was strongly upregulated in NS cHL fibroblasts, likely contributing to the accumulation of collagen in sclerotic bands of NS cHL. As previously shown for other types of cancer-associated fibroblasts, treatment by luteolin could reverse this fibroblast phenotype and decrease TIMP3 secretion. NS cHL fibroblasts showed enhanced proliferation when they were exposed to soluble factors released from HRS cells. For HRS cells, soluble factors from fibroblasts were not sufficient to protect them from Brentuximab-Vedotin induced cell death. However, HRS cells adherent to fibroblasts were protected from Brentuximab-Vedotin induced injury. In summary, we confirm the importance of fibroblasts for HRS cell survival and identify TIMP3 which probably contributes as a major factor to the typical fibrosis observed in NS cHL. classical hodgkin lymphoma nodular sclerosis fibroblasts gene expression analysis methylation profiling luteolin Neoplasms. Tumors. Oncology. Including cancer and carcinogens Claudia Döring verfasserin aut Adam Ustaszewski verfasserin aut Maciej Giefing verfasserin aut Marco Herling verfasserin aut Chiara Cencioni verfasserin aut Francesco Spallotta verfasserin aut Carlo Gaetano verfasserin aut Ralf Küppers verfasserin aut Martin-Leo Hansmann verfasserin aut Sylvia Hartmann verfasserin aut In Cancers MDPI AG, 2010 11(2019), 11, p 1687 (DE-627)614095670 (DE-600)2527080-1 20726694 nnns volume:11 year:2019 number:11, p 1687 https://doi.org/10.3390/cancers11111687 kostenfrei https://doaj.org/article/7f45eeec31804da08a3fa2d86ed999b5 kostenfrei https://www.mdpi.com/2072-6694/11/11/1687 kostenfrei https://doaj.org/toc/2072-6694 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 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_4338 GBV_ILN_4367 GBV_ILN_4700 AR 11 2019 11, p 1687
allfieldsSound	10.3390/cancers11111687 doi (DE-627)DOAJ060760087 (DE-599)DOAJ7f45eeec31804da08a3fa2d86ed999b5 DE-627 ger DE-627 rakwb eng RC254-282 Katrin Bankov verfasserin aut Fibroblasts in Nodular Sclerosing Classical Hodgkin Lymphoma Are Defined by a Specific Phenotype and Protect Tumor Cells from Brentuximab-Vedotin Induced Injury 2019 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Classical Hodgkin lymphoma (cHL) is one of the most common malignant lymphomas in Western Europe. The nodular sclerosing subtype of cHL (NS cHL) is characterized by a proliferation of fibroblasts in the tumor microenvironment, leading to fibrotic bands surrounding the lymphoma infiltrate. Several studies have described a crosstalk between the tumour cells of cHL, the Hodgkin- and Reed-Sternberg (HRS) cells, and cancer-associated fibroblasts. However, to date a deep molecular characterization of these fibroblasts is lacking. Thus, the aim of the present study is a comprehensive characterization of these fibroblasts. Gene expression profiling and methylation profiles of fibroblasts isolated from primary lymph node suspensions revealed persistent differences between fibroblasts obtained from NS cHL and lymphadenitis. NS cHL derived fibroblasts exhibit a myofibroblastic phenotype characterized by myocardin (<i<MYOCD</i<) expression. Moreover, <i<TIMP3</i<, an inhibitor of matrix metalloproteinases, was strongly upregulated in NS cHL fibroblasts, likely contributing to the accumulation of collagen in sclerotic bands of NS cHL. As previously shown for other types of cancer-associated fibroblasts, treatment by luteolin could reverse this fibroblast phenotype and decrease TIMP3 secretion. NS cHL fibroblasts showed enhanced proliferation when they were exposed to soluble factors released from HRS cells. For HRS cells, soluble factors from fibroblasts were not sufficient to protect them from Brentuximab-Vedotin induced cell death. However, HRS cells adherent to fibroblasts were protected from Brentuximab-Vedotin induced injury. In summary, we confirm the importance of fibroblasts for HRS cell survival and identify TIMP3 which probably contributes as a major factor to the typical fibrosis observed in NS cHL. classical hodgkin lymphoma nodular sclerosis fibroblasts gene expression analysis methylation profiling luteolin Neoplasms. Tumors. Oncology. Including cancer and carcinogens Claudia Döring verfasserin aut Adam Ustaszewski verfasserin aut Maciej Giefing verfasserin aut Marco Herling verfasserin aut Chiara Cencioni verfasserin aut Francesco Spallotta verfasserin aut Carlo Gaetano verfasserin aut Ralf Küppers verfasserin aut Martin-Leo Hansmann verfasserin aut Sylvia Hartmann verfasserin aut In Cancers MDPI AG, 2010 11(2019), 11, p 1687 (DE-627)614095670 (DE-600)2527080-1 20726694 nnns volume:11 year:2019 number:11, p 1687 https://doi.org/10.3390/cancers11111687 kostenfrei https://doaj.org/article/7f45eeec31804da08a3fa2d86ed999b5 kostenfrei https://www.mdpi.com/2072-6694/11/11/1687 kostenfrei https://doaj.org/toc/2072-6694 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 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_4338 GBV_ILN_4367 GBV_ILN_4700 AR 11 2019 11, p 1687
language	English
source	In Cancers 11(2019), 11, p 1687 volume:11 year:2019 number:11, p 1687
sourceStr	In Cancers 11(2019), 11, p 1687 volume:11 year:2019 number:11, p 1687
format_phy_str_mv	Article
institution	findex.gbv.de
topic_facet	classical hodgkin lymphoma nodular sclerosis fibroblasts gene expression analysis methylation profiling luteolin Neoplasms. Tumors. Oncology. Including cancer and carcinogens
isfreeaccess_bool	true
container_title	Cancers
authorswithroles_txt_mv	Katrin Bankov @@aut@@ Claudia Döring @@aut@@ Adam Ustaszewski @@aut@@ Maciej Giefing @@aut@@ Marco Herling @@aut@@ Chiara Cencioni @@aut@@ Francesco Spallotta @@aut@@ Carlo Gaetano @@aut@@ Ralf Küppers @@aut@@ Martin-Leo Hansmann @@aut@@ Sylvia Hartmann @@aut@@
publishDateDaySort_date	2019-01-01T00:00:00Z
hierarchy_top_id	614095670
id	DOAJ060760087
language_de	englisch
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callnumber-first	R - Medicine
author	Katrin Bankov
spellingShingle	Katrin Bankov misc RC254-282 misc classical hodgkin lymphoma misc nodular sclerosis misc fibroblasts misc gene expression analysis misc methylation profiling misc luteolin misc Neoplasms. Tumors. Oncology. Including cancer and carcinogens Fibroblasts in Nodular Sclerosing Classical Hodgkin Lymphoma Are Defined by a Specific Phenotype and Protect Tumor Cells from Brentuximab-Vedotin Induced Injury
authorStr	Katrin Bankov
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topic_title	RC254-282 Fibroblasts in Nodular Sclerosing Classical Hodgkin Lymphoma Are Defined by a Specific Phenotype and Protect Tumor Cells from Brentuximab-Vedotin Induced Injury classical hodgkin lymphoma nodular sclerosis fibroblasts gene expression analysis methylation profiling luteolin
topic	misc RC254-282 misc classical hodgkin lymphoma misc nodular sclerosis misc fibroblasts misc gene expression analysis misc methylation profiling misc luteolin misc Neoplasms. Tumors. Oncology. Including cancer and carcinogens
topic_unstemmed	misc RC254-282 misc classical hodgkin lymphoma misc nodular sclerosis misc fibroblasts misc gene expression analysis misc methylation profiling misc luteolin misc Neoplasms. Tumors. Oncology. Including cancer and carcinogens
topic_browse	misc RC254-282 misc classical hodgkin lymphoma misc nodular sclerosis misc fibroblasts misc gene expression analysis misc methylation profiling misc luteolin misc Neoplasms. Tumors. Oncology. Including cancer and carcinogens
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title	Fibroblasts in Nodular Sclerosing Classical Hodgkin Lymphoma Are Defined by a Specific Phenotype and Protect Tumor Cells from Brentuximab-Vedotin Induced Injury
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title_full	Fibroblasts in Nodular Sclerosing Classical Hodgkin Lymphoma Are Defined by a Specific Phenotype and Protect Tumor Cells from Brentuximab-Vedotin Induced Injury
author_sort	Katrin Bankov
journal	Cancers
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author_browse	Katrin Bankov Claudia Döring Adam Ustaszewski Maciej Giefing Marco Herling Chiara Cencioni Francesco Spallotta Carlo Gaetano Ralf Küppers Martin-Leo Hansmann Sylvia Hartmann
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author-letter	Katrin Bankov
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title_sort	fibroblasts in nodular sclerosing classical hodgkin lymphoma are defined by a specific phenotype and protect tumor cells from brentuximab-vedotin induced injury
callnumber	RC254-282
title_auth	Fibroblasts in Nodular Sclerosing Classical Hodgkin Lymphoma Are Defined by a Specific Phenotype and Protect Tumor Cells from Brentuximab-Vedotin Induced Injury
abstract	Classical Hodgkin lymphoma (cHL) is one of the most common malignant lymphomas in Western Europe. The nodular sclerosing subtype of cHL (NS cHL) is characterized by a proliferation of fibroblasts in the tumor microenvironment, leading to fibrotic bands surrounding the lymphoma infiltrate. Several studies have described a crosstalk between the tumour cells of cHL, the Hodgkin- and Reed-Sternberg (HRS) cells, and cancer-associated fibroblasts. However, to date a deep molecular characterization of these fibroblasts is lacking. Thus, the aim of the present study is a comprehensive characterization of these fibroblasts. Gene expression profiling and methylation profiles of fibroblasts isolated from primary lymph node suspensions revealed persistent differences between fibroblasts obtained from NS cHL and lymphadenitis. NS cHL derived fibroblasts exhibit a myofibroblastic phenotype characterized by myocardin (<i<MYOCD</i<) expression. Moreover, <i<TIMP3</i<, an inhibitor of matrix metalloproteinases, was strongly upregulated in NS cHL fibroblasts, likely contributing to the accumulation of collagen in sclerotic bands of NS cHL. As previously shown for other types of cancer-associated fibroblasts, treatment by luteolin could reverse this fibroblast phenotype and decrease TIMP3 secretion. NS cHL fibroblasts showed enhanced proliferation when they were exposed to soluble factors released from HRS cells. For HRS cells, soluble factors from fibroblasts were not sufficient to protect them from Brentuximab-Vedotin induced cell death. However, HRS cells adherent to fibroblasts were protected from Brentuximab-Vedotin induced injury. In summary, we confirm the importance of fibroblasts for HRS cell survival and identify TIMP3 which probably contributes as a major factor to the typical fibrosis observed in NS cHL.
abstractGer	Classical Hodgkin lymphoma (cHL) is one of the most common malignant lymphomas in Western Europe. The nodular sclerosing subtype of cHL (NS cHL) is characterized by a proliferation of fibroblasts in the tumor microenvironment, leading to fibrotic bands surrounding the lymphoma infiltrate. Several studies have described a crosstalk between the tumour cells of cHL, the Hodgkin- and Reed-Sternberg (HRS) cells, and cancer-associated fibroblasts. However, to date a deep molecular characterization of these fibroblasts is lacking. Thus, the aim of the present study is a comprehensive characterization of these fibroblasts. Gene expression profiling and methylation profiles of fibroblasts isolated from primary lymph node suspensions revealed persistent differences between fibroblasts obtained from NS cHL and lymphadenitis. NS cHL derived fibroblasts exhibit a myofibroblastic phenotype characterized by myocardin (<i<MYOCD</i<) expression. Moreover, <i<TIMP3</i<, an inhibitor of matrix metalloproteinases, was strongly upregulated in NS cHL fibroblasts, likely contributing to the accumulation of collagen in sclerotic bands of NS cHL. As previously shown for other types of cancer-associated fibroblasts, treatment by luteolin could reverse this fibroblast phenotype and decrease TIMP3 secretion. NS cHL fibroblasts showed enhanced proliferation when they were exposed to soluble factors released from HRS cells. For HRS cells, soluble factors from fibroblasts were not sufficient to protect them from Brentuximab-Vedotin induced cell death. However, HRS cells adherent to fibroblasts were protected from Brentuximab-Vedotin induced injury. In summary, we confirm the importance of fibroblasts for HRS cell survival and identify TIMP3 which probably contributes as a major factor to the typical fibrosis observed in NS cHL.
abstract_unstemmed	Classical Hodgkin lymphoma (cHL) is one of the most common malignant lymphomas in Western Europe. The nodular sclerosing subtype of cHL (NS cHL) is characterized by a proliferation of fibroblasts in the tumor microenvironment, leading to fibrotic bands surrounding the lymphoma infiltrate. Several studies have described a crosstalk between the tumour cells of cHL, the Hodgkin- and Reed-Sternberg (HRS) cells, and cancer-associated fibroblasts. However, to date a deep molecular characterization of these fibroblasts is lacking. Thus, the aim of the present study is a comprehensive characterization of these fibroblasts. Gene expression profiling and methylation profiles of fibroblasts isolated from primary lymph node suspensions revealed persistent differences between fibroblasts obtained from NS cHL and lymphadenitis. NS cHL derived fibroblasts exhibit a myofibroblastic phenotype characterized by myocardin (<i<MYOCD</i<) expression. Moreover, <i<TIMP3</i<, an inhibitor of matrix metalloproteinases, was strongly upregulated in NS cHL fibroblasts, likely contributing to the accumulation of collagen in sclerotic bands of NS cHL. As previously shown for other types of cancer-associated fibroblasts, treatment by luteolin could reverse this fibroblast phenotype and decrease TIMP3 secretion. NS cHL fibroblasts showed enhanced proliferation when they were exposed to soluble factors released from HRS cells. For HRS cells, soluble factors from fibroblasts were not sufficient to protect them from Brentuximab-Vedotin induced cell death. However, HRS cells adherent to fibroblasts were protected from Brentuximab-Vedotin induced injury. In summary, we confirm the importance of fibroblasts for HRS cell survival and identify TIMP3 which probably contributes as a major factor to the typical fibrosis observed in NS cHL.
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container_issue	11, p 1687
title_short	Fibroblasts in Nodular Sclerosing Classical Hodgkin Lymphoma Are Defined by a Specific Phenotype and Protect Tumor Cells from Brentuximab-Vedotin Induced Injury
url	https://doi.org/10.3390/cancers11111687 https://doaj.org/article/7f45eeec31804da08a3fa2d86ed999b5 https://www.mdpi.com/2072-6694/11/11/1687 https://doaj.org/toc/2072-6694
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author2	Claudia Döring Adam Ustaszewski Maciej Giefing Marco Herling Chiara Cencioni Francesco Spallotta Carlo Gaetano Ralf Küppers Martin-Leo Hansmann Sylvia Hartmann
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up_date	2024-07-03T16:51:59.839Z
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