Integrin alpha-V is an important driver in pancreatic adenocarcinoma progression

Abstract Background Mesothelial E- and P-selectins substantially mediate the intraperitoneal spread of Pancreatic ductal adenocarcinoma (PDA) cells in xenograft models. In the absence of selectins in the host, the integrin subunit alpha-V (ITGAV, CD51) was upregulated in the remaining metastatic dep...
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Autor*in:	Marius Kemper [verfasserIn] Alina Schiecke [verfasserIn] Hanna Maar [verfasserIn] Sergey Nikulin [verfasserIn] Andrey Poloznikov [verfasserIn] Vladimir Galatenko [verfasserIn] Michael Tachezy [verfasserIn] Florian Gebauer [verfasserIn] Tobias Lange [verfasserIn] Kristoffer Riecken [verfasserIn] Alexander Tonevitsky [verfasserIn] Achim Aigner [verfasserIn] Jakob Izbicki [verfasserIn] Udo Schumacher [verfasserIn] Daniel Wicklein [verfasserIn]

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2021

Schlagwörter:	Pancreatic cancer Integrin alpha-V Metastatic cascade TGF-beta signaling EMT

Übergeordnetes Werk:	In: Journal of Experimental & Clinical Cancer Research - BMC, 2008, 40(2021), 1, Seite 19
Übergeordnetes Werk:	volume:40 ; year:2021 ; number:1 ; pages:19

Links:	Link aufrufen Link aufrufen Link aufrufen Journal toc

DOI / URN:	10.1186/s13046-021-01946-2

Katalog-ID:	DOAJ019113536

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520			\|a Abstract Background Mesothelial E- and P-selectins substantially mediate the intraperitoneal spread of Pancreatic ductal adenocarcinoma (PDA) cells in xenograft models. In the absence of selectins in the host, the integrin subunit alpha-V (ITGAV, CD51) was upregulated in the remaining metastatic deposits. Here we present the first experimental study to investigate if ITGAV plays a functional role in PDA tumor growth and progression with a particular focus on intraperitoneal carcinomatosis. Methods Knockdown of ITGAV was generated using an RNA interference-mediated approach in two PDA cell lines. Tumor growth, intraperitoneal and distant metastasis were analyzed in a xenograft model. Cell lines were characterized in vitro. Gene expression of the xenograft tumors was analyzed. Patient samples were histologically classified and associations to survival were evaluated. Results The knockdown of ITGAV in PDA cells strongly reduces primary tumor growth, peritoneal carcinomatosis and spontaneous pulmonary metastasis. ITGAV activates latent TGF-β and thereby drives epithelial-mesenchymal transition. Combined depletion of ITGAV on the tumor cells and E- and P-selectins in the tumor-host synergistically almost abolishes intraperitoneal spread. Accordingly, high expression of ITGAV in PDA cells was associated with reduced survival in patients. Conclusion Combined depletion of ITGAV in PDA cells and E- and P-selectins in host mice massively suppresses intraperitoneal carcinomatosis of PDA cells xenografted into immunodeficient mice, confirming the hypothesis of a partly redundant adhesion cascade of metastasizing cancer cells. Our data strongly encourage developing novel therapeutic approaches for the combined targeting of E- and P-selectins and ITGAV in PDA.
650		4	\|a Pancreatic cancer
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650		4	\|a Metastatic cascade
650		4	\|a TGF-beta signaling
650		4	\|a EMT
653		0	\|a Neoplasms. Tumors. Oncology. Including cancer and carcinogens
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allfields	10.1186/s13046-021-01946-2 doi (DE-627)DOAJ019113536 (DE-599)DOAJ74ad8fbecb82403c9e846f168a4d146c DE-627 ger DE-627 rakwb eng RC254-282 Marius Kemper verfasserin aut Integrin alpha-V is an important driver in pancreatic adenocarcinoma progression 2021 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Background Mesothelial E- and P-selectins substantially mediate the intraperitoneal spread of Pancreatic ductal adenocarcinoma (PDA) cells in xenograft models. In the absence of selectins in the host, the integrin subunit alpha-V (ITGAV, CD51) was upregulated in the remaining metastatic deposits. Here we present the first experimental study to investigate if ITGAV plays a functional role in PDA tumor growth and progression with a particular focus on intraperitoneal carcinomatosis. Methods Knockdown of ITGAV was generated using an RNA interference-mediated approach in two PDA cell lines. Tumor growth, intraperitoneal and distant metastasis were analyzed in a xenograft model. Cell lines were characterized in vitro. Gene expression of the xenograft tumors was analyzed. Patient samples were histologically classified and associations to survival were evaluated. Results The knockdown of ITGAV in PDA cells strongly reduces primary tumor growth, peritoneal carcinomatosis and spontaneous pulmonary metastasis. ITGAV activates latent TGF-β and thereby drives epithelial-mesenchymal transition. Combined depletion of ITGAV on the tumor cells and E- and P-selectins in the tumor-host synergistically almost abolishes intraperitoneal spread. Accordingly, high expression of ITGAV in PDA cells was associated with reduced survival in patients. Conclusion Combined depletion of ITGAV in PDA cells and E- and P-selectins in host mice massively suppresses intraperitoneal carcinomatosis of PDA cells xenografted into immunodeficient mice, confirming the hypothesis of a partly redundant adhesion cascade of metastasizing cancer cells. Our data strongly encourage developing novel therapeutic approaches for the combined targeting of E- and P-selectins and ITGAV in PDA. Pancreatic cancer Integrin alpha-V Metastatic cascade TGF-beta signaling EMT Neoplasms. Tumors. Oncology. Including cancer and carcinogens Alina Schiecke verfasserin aut Hanna Maar verfasserin aut Sergey Nikulin verfasserin aut Andrey Poloznikov verfasserin aut Vladimir Galatenko verfasserin aut Michael Tachezy verfasserin aut Florian Gebauer verfasserin aut Tobias Lange verfasserin aut Kristoffer Riecken verfasserin aut Alexander Tonevitsky verfasserin aut Achim Aigner verfasserin aut Jakob Izbicki verfasserin aut Udo Schumacher verfasserin aut Daniel Wicklein verfasserin aut In Journal of Experimental & Clinical Cancer Research BMC, 2008 40(2021), 1, Seite 19 (DE-627)568921380 (DE-600)2430698-8 17569966 nnns volume:40 year:2021 number:1 pages:19 https://doi.org/10.1186/s13046-021-01946-2 kostenfrei https://doaj.org/article/74ad8fbecb82403c9e846f168a4d146c kostenfrei https://doi.org/10.1186/s13046-021-01946-2 kostenfrei https://doaj.org/toc/1756-9966 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_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_2003 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 40 2021 1 19
spelling	10.1186/s13046-021-01946-2 doi (DE-627)DOAJ019113536 (DE-599)DOAJ74ad8fbecb82403c9e846f168a4d146c DE-627 ger DE-627 rakwb eng RC254-282 Marius Kemper verfasserin aut Integrin alpha-V is an important driver in pancreatic adenocarcinoma progression 2021 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Background Mesothelial E- and P-selectins substantially mediate the intraperitoneal spread of Pancreatic ductal adenocarcinoma (PDA) cells in xenograft models. In the absence of selectins in the host, the integrin subunit alpha-V (ITGAV, CD51) was upregulated in the remaining metastatic deposits. Here we present the first experimental study to investigate if ITGAV plays a functional role in PDA tumor growth and progression with a particular focus on intraperitoneal carcinomatosis. Methods Knockdown of ITGAV was generated using an RNA interference-mediated approach in two PDA cell lines. Tumor growth, intraperitoneal and distant metastasis were analyzed in a xenograft model. Cell lines were characterized in vitro. Gene expression of the xenograft tumors was analyzed. Patient samples were histologically classified and associations to survival were evaluated. Results The knockdown of ITGAV in PDA cells strongly reduces primary tumor growth, peritoneal carcinomatosis and spontaneous pulmonary metastasis. ITGAV activates latent TGF-β and thereby drives epithelial-mesenchymal transition. Combined depletion of ITGAV on the tumor cells and E- and P-selectins in the tumor-host synergistically almost abolishes intraperitoneal spread. Accordingly, high expression of ITGAV in PDA cells was associated with reduced survival in patients. Conclusion Combined depletion of ITGAV in PDA cells and E- and P-selectins in host mice massively suppresses intraperitoneal carcinomatosis of PDA cells xenografted into immunodeficient mice, confirming the hypothesis of a partly redundant adhesion cascade of metastasizing cancer cells. Our data strongly encourage developing novel therapeutic approaches for the combined targeting of E- and P-selectins and ITGAV in PDA. Pancreatic cancer Integrin alpha-V Metastatic cascade TGF-beta signaling EMT Neoplasms. Tumors. Oncology. Including cancer and carcinogens Alina Schiecke verfasserin aut Hanna Maar verfasserin aut Sergey Nikulin verfasserin aut Andrey Poloznikov verfasserin aut Vladimir Galatenko verfasserin aut Michael Tachezy verfasserin aut Florian Gebauer verfasserin aut Tobias Lange verfasserin aut Kristoffer Riecken verfasserin aut Alexander Tonevitsky verfasserin aut Achim Aigner verfasserin aut Jakob Izbicki verfasserin aut Udo Schumacher verfasserin aut Daniel Wicklein verfasserin aut In Journal of Experimental & Clinical Cancer Research BMC, 2008 40(2021), 1, Seite 19 (DE-627)568921380 (DE-600)2430698-8 17569966 nnns volume:40 year:2021 number:1 pages:19 https://doi.org/10.1186/s13046-021-01946-2 kostenfrei https://doaj.org/article/74ad8fbecb82403c9e846f168a4d146c kostenfrei https://doi.org/10.1186/s13046-021-01946-2 kostenfrei https://doaj.org/toc/1756-9966 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_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_2003 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 40 2021 1 19
allfields_unstemmed	10.1186/s13046-021-01946-2 doi (DE-627)DOAJ019113536 (DE-599)DOAJ74ad8fbecb82403c9e846f168a4d146c DE-627 ger DE-627 rakwb eng RC254-282 Marius Kemper verfasserin aut Integrin alpha-V is an important driver in pancreatic adenocarcinoma progression 2021 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Background Mesothelial E- and P-selectins substantially mediate the intraperitoneal spread of Pancreatic ductal adenocarcinoma (PDA) cells in xenograft models. In the absence of selectins in the host, the integrin subunit alpha-V (ITGAV, CD51) was upregulated in the remaining metastatic deposits. Here we present the first experimental study to investigate if ITGAV plays a functional role in PDA tumor growth and progression with a particular focus on intraperitoneal carcinomatosis. Methods Knockdown of ITGAV was generated using an RNA interference-mediated approach in two PDA cell lines. Tumor growth, intraperitoneal and distant metastasis were analyzed in a xenograft model. Cell lines were characterized in vitro. Gene expression of the xenograft tumors was analyzed. Patient samples were histologically classified and associations to survival were evaluated. Results The knockdown of ITGAV in PDA cells strongly reduces primary tumor growth, peritoneal carcinomatosis and spontaneous pulmonary metastasis. ITGAV activates latent TGF-β and thereby drives epithelial-mesenchymal transition. Combined depletion of ITGAV on the tumor cells and E- and P-selectins in the tumor-host synergistically almost abolishes intraperitoneal spread. Accordingly, high expression of ITGAV in PDA cells was associated with reduced survival in patients. Conclusion Combined depletion of ITGAV in PDA cells and E- and P-selectins in host mice massively suppresses intraperitoneal carcinomatosis of PDA cells xenografted into immunodeficient mice, confirming the hypothesis of a partly redundant adhesion cascade of metastasizing cancer cells. Our data strongly encourage developing novel therapeutic approaches for the combined targeting of E- and P-selectins and ITGAV in PDA. Pancreatic cancer Integrin alpha-V Metastatic cascade TGF-beta signaling EMT Neoplasms. Tumors. Oncology. Including cancer and carcinogens Alina Schiecke verfasserin aut Hanna Maar verfasserin aut Sergey Nikulin verfasserin aut Andrey Poloznikov verfasserin aut Vladimir Galatenko verfasserin aut Michael Tachezy verfasserin aut Florian Gebauer verfasserin aut Tobias Lange verfasserin aut Kristoffer Riecken verfasserin aut Alexander Tonevitsky verfasserin aut Achim Aigner verfasserin aut Jakob Izbicki verfasserin aut Udo Schumacher verfasserin aut Daniel Wicklein verfasserin aut In Journal of Experimental & Clinical Cancer Research BMC, 2008 40(2021), 1, Seite 19 (DE-627)568921380 (DE-600)2430698-8 17569966 nnns volume:40 year:2021 number:1 pages:19 https://doi.org/10.1186/s13046-021-01946-2 kostenfrei https://doaj.org/article/74ad8fbecb82403c9e846f168a4d146c kostenfrei https://doi.org/10.1186/s13046-021-01946-2 kostenfrei https://doaj.org/toc/1756-9966 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_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_2003 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 40 2021 1 19
allfieldsGer	10.1186/s13046-021-01946-2 doi (DE-627)DOAJ019113536 (DE-599)DOAJ74ad8fbecb82403c9e846f168a4d146c DE-627 ger DE-627 rakwb eng RC254-282 Marius Kemper verfasserin aut Integrin alpha-V is an important driver in pancreatic adenocarcinoma progression 2021 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Background Mesothelial E- and P-selectins substantially mediate the intraperitoneal spread of Pancreatic ductal adenocarcinoma (PDA) cells in xenograft models. In the absence of selectins in the host, the integrin subunit alpha-V (ITGAV, CD51) was upregulated in the remaining metastatic deposits. Here we present the first experimental study to investigate if ITGAV plays a functional role in PDA tumor growth and progression with a particular focus on intraperitoneal carcinomatosis. Methods Knockdown of ITGAV was generated using an RNA interference-mediated approach in two PDA cell lines. Tumor growth, intraperitoneal and distant metastasis were analyzed in a xenograft model. Cell lines were characterized in vitro. Gene expression of the xenograft tumors was analyzed. Patient samples were histologically classified and associations to survival were evaluated. Results The knockdown of ITGAV in PDA cells strongly reduces primary tumor growth, peritoneal carcinomatosis and spontaneous pulmonary metastasis. ITGAV activates latent TGF-β and thereby drives epithelial-mesenchymal transition. Combined depletion of ITGAV on the tumor cells and E- and P-selectins in the tumor-host synergistically almost abolishes intraperitoneal spread. Accordingly, high expression of ITGAV in PDA cells was associated with reduced survival in patients. Conclusion Combined depletion of ITGAV in PDA cells and E- and P-selectins in host mice massively suppresses intraperitoneal carcinomatosis of PDA cells xenografted into immunodeficient mice, confirming the hypothesis of a partly redundant adhesion cascade of metastasizing cancer cells. Our data strongly encourage developing novel therapeutic approaches for the combined targeting of E- and P-selectins and ITGAV in PDA. Pancreatic cancer Integrin alpha-V Metastatic cascade TGF-beta signaling EMT Neoplasms. Tumors. Oncology. Including cancer and carcinogens Alina Schiecke verfasserin aut Hanna Maar verfasserin aut Sergey Nikulin verfasserin aut Andrey Poloznikov verfasserin aut Vladimir Galatenko verfasserin aut Michael Tachezy verfasserin aut Florian Gebauer verfasserin aut Tobias Lange verfasserin aut Kristoffer Riecken verfasserin aut Alexander Tonevitsky verfasserin aut Achim Aigner verfasserin aut Jakob Izbicki verfasserin aut Udo Schumacher verfasserin aut Daniel Wicklein verfasserin aut In Journal of Experimental & Clinical Cancer Research BMC, 2008 40(2021), 1, Seite 19 (DE-627)568921380 (DE-600)2430698-8 17569966 nnns volume:40 year:2021 number:1 pages:19 https://doi.org/10.1186/s13046-021-01946-2 kostenfrei https://doaj.org/article/74ad8fbecb82403c9e846f168a4d146c kostenfrei https://doi.org/10.1186/s13046-021-01946-2 kostenfrei https://doaj.org/toc/1756-9966 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_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_2003 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 40 2021 1 19
allfieldsSound	10.1186/s13046-021-01946-2 doi (DE-627)DOAJ019113536 (DE-599)DOAJ74ad8fbecb82403c9e846f168a4d146c DE-627 ger DE-627 rakwb eng RC254-282 Marius Kemper verfasserin aut Integrin alpha-V is an important driver in pancreatic adenocarcinoma progression 2021 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Background Mesothelial E- and P-selectins substantially mediate the intraperitoneal spread of Pancreatic ductal adenocarcinoma (PDA) cells in xenograft models. In the absence of selectins in the host, the integrin subunit alpha-V (ITGAV, CD51) was upregulated in the remaining metastatic deposits. Here we present the first experimental study to investigate if ITGAV plays a functional role in PDA tumor growth and progression with a particular focus on intraperitoneal carcinomatosis. Methods Knockdown of ITGAV was generated using an RNA interference-mediated approach in two PDA cell lines. Tumor growth, intraperitoneal and distant metastasis were analyzed in a xenograft model. Cell lines were characterized in vitro. Gene expression of the xenograft tumors was analyzed. Patient samples were histologically classified and associations to survival were evaluated. Results The knockdown of ITGAV in PDA cells strongly reduces primary tumor growth, peritoneal carcinomatosis and spontaneous pulmonary metastasis. ITGAV activates latent TGF-β and thereby drives epithelial-mesenchymal transition. Combined depletion of ITGAV on the tumor cells and E- and P-selectins in the tumor-host synergistically almost abolishes intraperitoneal spread. Accordingly, high expression of ITGAV in PDA cells was associated with reduced survival in patients. Conclusion Combined depletion of ITGAV in PDA cells and E- and P-selectins in host mice massively suppresses intraperitoneal carcinomatosis of PDA cells xenografted into immunodeficient mice, confirming the hypothesis of a partly redundant adhesion cascade of metastasizing cancer cells. Our data strongly encourage developing novel therapeutic approaches for the combined targeting of E- and P-selectins and ITGAV in PDA. Pancreatic cancer Integrin alpha-V Metastatic cascade TGF-beta signaling EMT Neoplasms. Tumors. Oncology. Including cancer and carcinogens Alina Schiecke verfasserin aut Hanna Maar verfasserin aut Sergey Nikulin verfasserin aut Andrey Poloznikov verfasserin aut Vladimir Galatenko verfasserin aut Michael Tachezy verfasserin aut Florian Gebauer verfasserin aut Tobias Lange verfasserin aut Kristoffer Riecken verfasserin aut Alexander Tonevitsky verfasserin aut Achim Aigner verfasserin aut Jakob Izbicki verfasserin aut Udo Schumacher verfasserin aut Daniel Wicklein verfasserin aut In Journal of Experimental & Clinical Cancer Research BMC, 2008 40(2021), 1, Seite 19 (DE-627)568921380 (DE-600)2430698-8 17569966 nnns volume:40 year:2021 number:1 pages:19 https://doi.org/10.1186/s13046-021-01946-2 kostenfrei https://doaj.org/article/74ad8fbecb82403c9e846f168a4d146c kostenfrei https://doi.org/10.1186/s13046-021-01946-2 kostenfrei https://doaj.org/toc/1756-9966 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_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_2003 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 40 2021 1 19
language	English
source	In Journal of Experimental & Clinical Cancer Research 40(2021), 1, Seite 19 volume:40 year:2021 number:1 pages:19
sourceStr	In Journal of Experimental & Clinical Cancer Research 40(2021), 1, Seite 19 volume:40 year:2021 number:1 pages:19
format_phy_str_mv	Article
institution	findex.gbv.de
topic_facet	Pancreatic cancer Integrin alpha-V Metastatic cascade TGF-beta signaling EMT Neoplasms. Tumors. Oncology. Including cancer and carcinogens
isfreeaccess_bool	true
container_title	Journal of Experimental & Clinical Cancer Research
authorswithroles_txt_mv	Marius Kemper @@aut@@ Alina Schiecke @@aut@@ Hanna Maar @@aut@@ Sergey Nikulin @@aut@@ Andrey Poloznikov @@aut@@ Vladimir Galatenko @@aut@@ Michael Tachezy @@aut@@ Florian Gebauer @@aut@@ Tobias Lange @@aut@@ Kristoffer Riecken @@aut@@ Alexander Tonevitsky @@aut@@ Achim Aigner @@aut@@ Jakob Izbicki @@aut@@ Udo Schumacher @@aut@@ Daniel Wicklein @@aut@@
publishDateDaySort_date	2021-01-01T00:00:00Z
hierarchy_top_id	568921380
id	DOAJ019113536
language_de	englisch
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callnumber-first	R - Medicine
author	Marius Kemper
spellingShingle	Marius Kemper misc RC254-282 misc Pancreatic cancer misc Integrin alpha-V misc Metastatic cascade misc TGF-beta signaling misc EMT misc Neoplasms. Tumors. Oncology. Including cancer and carcinogens Integrin alpha-V is an important driver in pancreatic adenocarcinoma progression
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topic_title	RC254-282 Integrin alpha-V is an important driver in pancreatic adenocarcinoma progression Pancreatic cancer Integrin alpha-V Metastatic cascade TGF-beta signaling EMT
topic	misc RC254-282 misc Pancreatic cancer misc Integrin alpha-V misc Metastatic cascade misc TGF-beta signaling misc EMT misc Neoplasms. Tumors. Oncology. Including cancer and carcinogens
topic_unstemmed	misc RC254-282 misc Pancreatic cancer misc Integrin alpha-V misc Metastatic cascade misc TGF-beta signaling misc EMT misc Neoplasms. Tumors. Oncology. Including cancer and carcinogens
topic_browse	misc RC254-282 misc Pancreatic cancer misc Integrin alpha-V misc Metastatic cascade misc TGF-beta signaling misc EMT misc Neoplasms. Tumors. Oncology. Including cancer and carcinogens
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title	Integrin alpha-V is an important driver in pancreatic adenocarcinoma progression
ctrlnum	(DE-627)DOAJ019113536 (DE-599)DOAJ74ad8fbecb82403c9e846f168a4d146c
title_full	Integrin alpha-V is an important driver in pancreatic adenocarcinoma progression
author_sort	Marius Kemper
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author_browse	Marius Kemper Alina Schiecke Hanna Maar Sergey Nikulin Andrey Poloznikov Vladimir Galatenko Michael Tachezy Florian Gebauer Tobias Lange Kristoffer Riecken Alexander Tonevitsky Achim Aigner Jakob Izbicki Udo Schumacher Daniel Wicklein
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title_sort	integrin alpha-v is an important driver in pancreatic adenocarcinoma progression
callnumber	RC254-282
title_auth	Integrin alpha-V is an important driver in pancreatic adenocarcinoma progression
abstract	Abstract Background Mesothelial E- and P-selectins substantially mediate the intraperitoneal spread of Pancreatic ductal adenocarcinoma (PDA) cells in xenograft models. In the absence of selectins in the host, the integrin subunit alpha-V (ITGAV, CD51) was upregulated in the remaining metastatic deposits. Here we present the first experimental study to investigate if ITGAV plays a functional role in PDA tumor growth and progression with a particular focus on intraperitoneal carcinomatosis. Methods Knockdown of ITGAV was generated using an RNA interference-mediated approach in two PDA cell lines. Tumor growth, intraperitoneal and distant metastasis were analyzed in a xenograft model. Cell lines were characterized in vitro. Gene expression of the xenograft tumors was analyzed. Patient samples were histologically classified and associations to survival were evaluated. Results The knockdown of ITGAV in PDA cells strongly reduces primary tumor growth, peritoneal carcinomatosis and spontaneous pulmonary metastasis. ITGAV activates latent TGF-β and thereby drives epithelial-mesenchymal transition. Combined depletion of ITGAV on the tumor cells and E- and P-selectins in the tumor-host synergistically almost abolishes intraperitoneal spread. Accordingly, high expression of ITGAV in PDA cells was associated with reduced survival in patients. Conclusion Combined depletion of ITGAV in PDA cells and E- and P-selectins in host mice massively suppresses intraperitoneal carcinomatosis of PDA cells xenografted into immunodeficient mice, confirming the hypothesis of a partly redundant adhesion cascade of metastasizing cancer cells. Our data strongly encourage developing novel therapeutic approaches for the combined targeting of E- and P-selectins and ITGAV in PDA.
abstractGer	Abstract Background Mesothelial E- and P-selectins substantially mediate the intraperitoneal spread of Pancreatic ductal adenocarcinoma (PDA) cells in xenograft models. In the absence of selectins in the host, the integrin subunit alpha-V (ITGAV, CD51) was upregulated in the remaining metastatic deposits. Here we present the first experimental study to investigate if ITGAV plays a functional role in PDA tumor growth and progression with a particular focus on intraperitoneal carcinomatosis. Methods Knockdown of ITGAV was generated using an RNA interference-mediated approach in two PDA cell lines. Tumor growth, intraperitoneal and distant metastasis were analyzed in a xenograft model. Cell lines were characterized in vitro. Gene expression of the xenograft tumors was analyzed. Patient samples were histologically classified and associations to survival were evaluated. Results The knockdown of ITGAV in PDA cells strongly reduces primary tumor growth, peritoneal carcinomatosis and spontaneous pulmonary metastasis. ITGAV activates latent TGF-β and thereby drives epithelial-mesenchymal transition. Combined depletion of ITGAV on the tumor cells and E- and P-selectins in the tumor-host synergistically almost abolishes intraperitoneal spread. Accordingly, high expression of ITGAV in PDA cells was associated with reduced survival in patients. Conclusion Combined depletion of ITGAV in PDA cells and E- and P-selectins in host mice massively suppresses intraperitoneal carcinomatosis of PDA cells xenografted into immunodeficient mice, confirming the hypothesis of a partly redundant adhesion cascade of metastasizing cancer cells. Our data strongly encourage developing novel therapeutic approaches for the combined targeting of E- and P-selectins and ITGAV in PDA.
abstract_unstemmed	Abstract Background Mesothelial E- and P-selectins substantially mediate the intraperitoneal spread of Pancreatic ductal adenocarcinoma (PDA) cells in xenograft models. In the absence of selectins in the host, the integrin subunit alpha-V (ITGAV, CD51) was upregulated in the remaining metastatic deposits. Here we present the first experimental study to investigate if ITGAV plays a functional role in PDA tumor growth and progression with a particular focus on intraperitoneal carcinomatosis. Methods Knockdown of ITGAV was generated using an RNA interference-mediated approach in two PDA cell lines. Tumor growth, intraperitoneal and distant metastasis were analyzed in a xenograft model. Cell lines were characterized in vitro. Gene expression of the xenograft tumors was analyzed. Patient samples were histologically classified and associations to survival were evaluated. Results The knockdown of ITGAV in PDA cells strongly reduces primary tumor growth, peritoneal carcinomatosis and spontaneous pulmonary metastasis. ITGAV activates latent TGF-β and thereby drives epithelial-mesenchymal transition. Combined depletion of ITGAV on the tumor cells and E- and P-selectins in the tumor-host synergistically almost abolishes intraperitoneal spread. Accordingly, high expression of ITGAV in PDA cells was associated with reduced survival in patients. Conclusion Combined depletion of ITGAV in PDA cells and E- and P-selectins in host mice massively suppresses intraperitoneal carcinomatosis of PDA cells xenografted into immunodeficient mice, confirming the hypothesis of a partly redundant adhesion cascade of metastasizing cancer cells. Our data strongly encourage developing novel therapeutic approaches for the combined targeting of E- and P-selectins and ITGAV in PDA.
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title_short	Integrin alpha-V is an important driver in pancreatic adenocarcinoma progression
url	https://doi.org/10.1186/s13046-021-01946-2 https://doaj.org/article/74ad8fbecb82403c9e846f168a4d146c https://doaj.org/toc/1756-9966
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author2	Alina Schiecke Hanna Maar Sergey Nikulin Andrey Poloznikov Vladimir Galatenko Michael Tachezy Florian Gebauer Tobias Lange Kristoffer Riecken Alexander Tonevitsky Achim Aigner Jakob Izbicki Udo Schumacher Daniel Wicklein
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