Silencing of TGF-β1 in tumor cells impacts MMP-9 in tumor microenvironment

Abstract Transforming growth factor (TGF)-β1 contributes to autocrine and paracrine functions in the tumor microenvironment (TME). The present study examined the effects of TGF-β1 crosstalk in TME and its role in mediating tumor formation and progression by targeted abrogation of TGF-β1 expression i...

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Autores principales:	Lakisha D. Moore-Smith, Tatyana Isayeva, Joo Hyoung Lee, Andra Frost, Selvarangan Ponnazhagan
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/df50d61f90da4eb596f8bb21be034591
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spelling	oai:doaj.org-article:df50d61f90da4eb596f8bb21be0345912021-12-02T15:06:01ZSilencing of TGF-β1 in tumor cells impacts MMP-9 in tumor microenvironment10.1038/s41598-017-09062-y2045-2322https://doaj.org/article/df50d61f90da4eb596f8bb21be0345912017-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-09062-yhttps://doaj.org/toc/2045-2322Abstract Transforming growth factor (TGF)-β1 contributes to autocrine and paracrine functions in the tumor microenvironment (TME). The present study examined the effects of TGF-β1 crosstalk in TME and its role in mediating tumor formation and progression by targeted abrogation of TGF-β1 expression in metastatic cells in situ. Using species-specific primers, we found a significant increase in MMP-9 gene expression in the tumor-reactive stroma during late-stage metastasis in the lung. This effect was also confirmed in cancer-associated fibroblasts (CAFs) when co-cultured with the tumor cells. Knockdown of TGF-β1 expression in the tumor cells negatively affected matrix metalloproteinase (MMP)-9 gene expression. Fibroblasts, cultured in the presence of tumor cells with intact TGF-β1, showed a significant increase in proliferation rate, as well as expression of VEGF, bFGF, and SDF-1, which was not seen when TGF-β1 expression was abrogated in tumor cells. Absence of TGF-β1 in tumor cells also failed to result in myofibroblast differentiation. Co-implantation of CAFs and tumor cells with either intact TGF-β1 expression or devoid of TGF-β1 in vivo showed a significant increase in tumor growth kinetics in both cell types, suggesting a possible activation TGF-β receptor signaling in tumor cells in response to TGF-β from the TME.Lakisha D. Moore-SmithTatyana IsayevaJoo Hyoung LeeAndra FrostSelvarangan PonnazhaganNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-10 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Lakisha D. Moore-Smith Tatyana Isayeva Joo Hyoung Lee Andra Frost Selvarangan Ponnazhagan Silencing of TGF-β1 in tumor cells impacts MMP-9 in tumor microenvironment
description	Abstract Transforming growth factor (TGF)-β1 contributes to autocrine and paracrine functions in the tumor microenvironment (TME). The present study examined the effects of TGF-β1 crosstalk in TME and its role in mediating tumor formation and progression by targeted abrogation of TGF-β1 expression in metastatic cells in situ. Using species-specific primers, we found a significant increase in MMP-9 gene expression in the tumor-reactive stroma during late-stage metastasis in the lung. This effect was also confirmed in cancer-associated fibroblasts (CAFs) when co-cultured with the tumor cells. Knockdown of TGF-β1 expression in the tumor cells negatively affected matrix metalloproteinase (MMP)-9 gene expression. Fibroblasts, cultured in the presence of tumor cells with intact TGF-β1, showed a significant increase in proliferation rate, as well as expression of VEGF, bFGF, and SDF-1, which was not seen when TGF-β1 expression was abrogated in tumor cells. Absence of TGF-β1 in tumor cells also failed to result in myofibroblast differentiation. Co-implantation of CAFs and tumor cells with either intact TGF-β1 expression or devoid of TGF-β1 in vivo showed a significant increase in tumor growth kinetics in both cell types, suggesting a possible activation TGF-β receptor signaling in tumor cells in response to TGF-β from the TME.
format	article
author	Lakisha D. Moore-Smith Tatyana Isayeva Joo Hyoung Lee Andra Frost Selvarangan Ponnazhagan
author_facet	Lakisha D. Moore-Smith Tatyana Isayeva Joo Hyoung Lee Andra Frost Selvarangan Ponnazhagan
author_sort	Lakisha D. Moore-Smith
title	Silencing of TGF-β1 in tumor cells impacts MMP-9 in tumor microenvironment
title_short	Silencing of TGF-β1 in tumor cells impacts MMP-9 in tumor microenvironment
title_full	Silencing of TGF-β1 in tumor cells impacts MMP-9 in tumor microenvironment
title_fullStr	Silencing of TGF-β1 in tumor cells impacts MMP-9 in tumor microenvironment
title_full_unstemmed	Silencing of TGF-β1 in tumor cells impacts MMP-9 in tumor microenvironment
title_sort	silencing of tgf-β1 in tumor cells impacts mmp-9 in tumor microenvironment
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/df50d61f90da4eb596f8bb21be034591
work_keys_str_mv	AT lakishadmooresmith silencingoftgfb1intumorcellsimpactsmmp9intumormicroenvironment AT tatyanaisayeva silencingoftgfb1intumorcellsimpactsmmp9intumormicroenvironment AT joohyounglee silencingoftgfb1intumorcellsimpactsmmp9intumormicroenvironment AT andrafrost silencingoftgfb1intumorcellsimpactsmmp9intumormicroenvironment AT selvaranganponnazhagan silencingoftgfb1intumorcellsimpactsmmp9intumormicroenvironment
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Silencing of TGF-β1 in tumor cells impacts MMP-9 in tumor microenvironment

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