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

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 metasta...

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Detalles Bibliográficos
Autores principales: Moore-Smith, Lakisha D., Isayeva, Tatyana, Lee, Joo Hyoung, Frost, Andra, Ponnazhagan, Selvarangan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5561077/
https://www.ncbi.nlm.nih.gov/pubmed/28819116
http://dx.doi.org/10.1038/s41598-017-09062-y
Descripción
Sumario: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.