PHENOTYPES OF HUMAN ESOPHAGEAL SQUAMOUS-CELL CARCINOMA BASED ON MATRIX METALLOPROTEINASE PRODUCTION

We investigated the effects of epidermal growth factor (EGF) and trans forming growth factor-beta (TGF-beta) on cell growth and on regulation of matrix metalloproteinases (MMPs) in four cell lines of human esoph ageal squamous cell carcinomas (TE8, TE9, TE10, and TE11). EGF stimula ted the production of proforms of gelatinase B (MMP-9) by three cell l ines that could synthesize EGF by themselves, with TE9 being the excep tion. Particularly, both the production of MMP-9 and DNA synthesis in TE10 were stimulated significantly by EGF. TGF-beta slightly stimulate d DNA synthesis in two cell lines, TE9 and TE11, and TGF-beta secretio n by TE9 was detected. The production of proforms of gelatinases A (MM P-2) and MMP-9 was gradually induced by TGF-beta in a concentration-de pendent manner in all the cell lines except for TE9. Flow cytometric a nalysis revealed that all the lines expressed both EGF- and TGF-beta-r eceptors. In conclusion, our present results indicate that at least th ere are possibly two distinct phenotypes in human esophageal squamous cell carcinoma: one (TE10) depends on autocrine EGF production that en hances DNA synthesis and MMP-9 production; and the other (TE9) on auto crine TGF-beta that stimulates DNA synthesis but not in relation to ge latinase production.