MODULATION OF FIBRONECTIN SYNTHESIS BY CANCER CELL-FIBROBLAST INTERACTION - CANCER-CELLS STIMULATE FIBRONECTIN PRODUCTION AND AFFECT ALTERNATIVE SPLICING OF FIBRONECTIN PRE-MESSENGER-RNA AT EDA REGION IN FIBROBLASTS

Conditioned medium (CM) of human rectal adenocarcinoma cell line RCM-1 stimulated both cellular (c-) and plasma (p-) fibronectin (FN) produc tion by human fibroblasts and modulated the alternative splicing of it s primary transcript at the EDA region to express more EDA-containing (+) mRNA. This EDA(+) mRNA-stimulating effect of CM was inhibited by t reatment with an anti-human transforming growth factor (TGF)-beta anti body. TGF-beta production by RCM-1 cells was demonstrated by immunoblo tting and RT-PCR. Thus, FN synthesis and splicing-in at the EDA region in fibroblasts were stimulated by cancer cells predominantly via TGF- beta. Since RCM-1 cells adhered to cFN, which contains EDA, more effic iently than pFN and adhesion to extracellular matrix proteins such as FN is the first step to migration, the cancer stroma modulated by canc er cell-fibroblast interaction may facilitate cancer invasion.