Fibroblast and prostate tumor cell cross-talk: Fibroblast differentiation, TGF-beta, and extracellular matrix down-regulation

Autor(es)

Coulson-Thomas, Vivien J. ^[1] ; Gesteira, Tarsis F. ; Coulson-Thomas, Yvette M. ; Vicente, Carolina M. ; Tersariol, Ivarne L. S. ; Nader, Helena B. ; Toma, Leny

Afiliação do(s) autor(es)

^[1] Univ Fed Sao Paulo, Dept Bioquim, Escola Paulista Med, BR-04044020 Sao Paulo - Brazil

• Tipo de documento: Artigo Científico
• Fonte: Experimental Cell Research; v. 316, n. 19, p. 3207-3226, NOV 15 2010.
• Citações Web of Science: 42

Resumo

Growth and survival of tumors at a site of metastasis involve interactions with stromal cells in the surrounding environment. Stromal cells aid tumor cell growth by producing cytokines as well as by modifying the environment surrounding the tumor through modulation of the extracellular matrix (ECM). Small leucine-rich proteoglycans (SLRPs) are biologically active components of the ECM which can be altered in the stroma surrounding tumors. The influence tumor cells have on stromal cells has been well elucidated. However, little is understood about the effect metastatic cancer cells have on the cell biology and behavior of the local stromal cells. Our data reveal a significant downregulation in the expression of ECM components such as collagens I, II, III, and IV, and the SLRPs, decorin, biglycan, lumican, and fibromodulin in stromal cells when grown in the presence of two metastatic prostate cancer cell lines PO and DU145. Interestingly, TGF-beta down-regulation was observed in stromal cells, as well as actin depolymerization and increased vimentin and alpha 5 beta 1 integrin expression. MT1-MMP expression was upregulated and localized in stromal cell protrusions which extended into the ECM. Moreover, enhanced stromal cell migration was observed after crosstalk with metastatic prostate tumor cells. Xenografting metastatic prostate cancer cells together with ``activated{''} stromal cells led to increased tumorigenicity of the prostate cancer cells. Our findings suggest that metastatic prostate cancer cells create a metastatic niche by altering the phenotype of local stromal cells, leading to changes in the ECM. (C) 2010 Elsevier Inc. All rights reserved. (AU)

• Processo FAPESP: 07/59801-1 - Estudo do envolvimento dos proteoglicanos na interacao entre celulas tumorais e estromais na formacao do tumor coloretal e de prostata
• Beneficiário: Leny Toma
• Modalidade de apoio: Auxílio à Pesquisa - Regular