Culturing of stromal cells with HCT116 cells in high density tumor microenvironment co-cultures resulted in an increase of TGF-β expression and Smad2 phosphorylation in HCT116 compared to high density tumor mono-cultures, and this response was considerably blocked by the neutralizing pan-TGF-β antibody (Fig. 7C-D), but not by control IgG (not shown). This evidence concerns the gene SMAD2 and neoplasm.