Epithelial cancer cell invasion is facilitated by stromal cells, immune cells, endothelial cells and other epithelial cells. We have used two human papilloma immortalized prostate cell lines, CA-HPV-10 from a carcinoma and PZ-HPV-7 cells from normal prostatic epithelium to study cell-cell influences on growth, gelatinase secretion, invasion and responses to TGFbeta1. We found that co-culture with CA-10 carcinoma cells stimulates proliferation of the PZ-7 epithelial line. TGFbeta1 inhibited growth of both lines, but while inhibitory effects on the CA-10 cells diminished after removal of the peptide, inhibition of PZ-7 was lasting. Interestingly, the TGFbeta-induced growth inhibition in PZ-7 cells could be partially reversed by co-culture with CA-10 cells. Co-culture with CA cells in a 3-chamber invasion assay also promoted invasion of PZ cells. CA-10 invasion was enhanced by co-culture with TGFbeta1-treated-PZ-7 cultures and this enhancement was associated with TGFbeta1-induced secretion of matrix metalloproteinase-9. Our observations suggest that interaction between prostate cancer cells and prostate epithelial cells may promote proliferation of the epithelial cell population and produce a paracrine source of MMP-9 which may facilitate early cancer cell invasion.