Conditioned medium (CM) of human rectal adenocarcinoma cell line RCM-1 stimulated both cellular (c-) and plasma (p-) fibronectin (FN) production by human fibroblasts and modulated the alternative splicing of its primary transcript at the EDA region to express more EDA-containing (+) mRNA. This EDA(+) mRNA-stimulating effect of CM was inhibited by treatment with an anti-human transforming growth factor (TGF)-beta antibody. TGF-beta production by RCM-1 cells was demonstrated by immunoblotting 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 efficiently than pFN and adhesion to extracellular matrix proteins such as FN is the first step to migration, the cancer stroma modulated by cancer cell-fibroblast interaction may facilitate cancer invasion.

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