Fibroblast’s role in breast cancer: a proteomic approach

Abstract

Fibroblasts are the major mesenchymal cell types committed to the matrix formation and renewal. Moreover they are the main source of paracrine factors that influence the growth of epithelial cells of neighbouring tissues. For these properties they may be involved in tumourigenesis, either by remodelling the tumor-associated extracellular matrix (ECM), and by the production of paracrine factors that influence the growth of carcinoma cells. Studies on fibroblasts associated to carcinomas have documented their phenotypic modifications, including abnormal migratory behaviour in vitro and growth factors altered expression(Schor & Schor, 2001). In addition, fibroblasts often recruit inflammatory cells involved in the stimulation of angiogenesis, probably by the proteolytic release of sequestered angiogenic activators (Tlsty & Hein, 2001). Reciprocally, cancer cells may regulate the biosynthetic activities of fibroblasts, thus altering the ECM of the tumor, which in turn exerts some influence on neoplastic cell behaviour. The aim of the present work was to extend our previous observations on the effects of microenvironment factors on neoplastic cell behaviour (Pucci-Minafra et al.2008,in press), utilizing the well characterized breast cancer-derived cells, 8701-BC (Minafra et al. 1989). The neoplastic cells were exposed to influences of fibroblasts either in a co-culture system or through incubation with the theirs conditioned media. In this report we show that the fibroblasts affect neoplastic cell behaviour by: increasing cell proliferation rate, rising the migration and invasion properties of cells in boyden chamber assays, and inducing a transition of cytoskeletal filament expression. Further, these data were confirmed by proteomic approach that allow to evaluate multiple response of cells subjected to external influences.