Biological implications of growth factors on the mechanism of invasion in gynecological tumor cells

We investigated the effects of epidermal growth factor (EGF) and transformi ng growth factor-alpha (TGF-alpha) on migration, invasion and proteinase ex pression of gynecological cultured cancer cells (SKG-IIIb cervical squamous cell carcinoma, OMC-4 cervical adenocarcinoma, SNG-M endometrial adenocarc inoma and OMC-3 ovarian adenocarcinoma), and whether these growth factors a ffect thymidine phosphorylase/platelet-derived endothelial cell growth fact or expression of tumor cells. Tumor cell migration along a gradient of subs tratum-bound fibronectin and invasion into reconstituted basement membrane were stimulated by 0.1-10 nM EGF and TGF-alpha in a concentration-dependent manner. The zymography of tumor-conditioned medium showed that the treatme nt of tumor cells with EGF and TGF-a resulted in the increase of type IV co llagenases, stromelysin and urokinase-type plasminogen activator which was partly confirmed by immunoblot analysis. The expression of thymidine phosph orylase/platelet-derived endothelial cell growth factor which has angiogeni c activity, was also upregulated by these growth factors. These results sug gest that EGF and TGF-alpha act as positive regulators on the invasion proc ess of gynecological tumor cells which may be associated with their stimula tory action on the motility of tumor cells, the expression of proteinases s ecreted by tumor cells and the angiogenic phenotype.