STROMELYSIN-3 EXPRESSION PROMOTES TUMOR TAKE IN NUDE-MICE

Stromelysin-3 (ST3) is a matrix metalloproteinase expressed in human c arcinomas in ways suggesting that it may play a role in tumor progress ion. To test this possibility, we have performed gene transfer experim ents using both anti-sense and sense ST3 expression vectors, and malig nant cells either expressing (NIH 3T3 fibroblasts) or not (MCF7 epithe lial cells) endogenous ST3, We have compared the ability of parental a nd transfected cells to cause subcutaneous tumor development in nude m ice, 3T3 cells expressing anti-sense ST3 RNA showed reduced tumorigeni city, and MCF7 cells expressing mouse or human ST3 were associated wit h reduced tumor-free period leading to a significant increased tumor i ncidence (P < 10(-4)), However, once established, the ST3-expressing t umors did not grow faster than those obtained with the parental MCF7 c ell line. In addition, tumors obtained after sub-cutaneous injection o f ST3-expressing or nonexpressing cells did not exhibit obvious histol ogical differences, and careful examination did not reveal any local i nvasive tissue areas nor systemic metastases, These in vivo observatio ns were in agreement with those obtained in vitro showing that ST3 exp ression did not modify proliferative nor invasive properties of transf ected cells, Altogether, these results indicate that ST3 expression pr omotes tumor take in nude mice, presumably by favoring cancer cell sur vival in a tissue environment initially not permissive for tumor growt h, These findings represent the first experimental evidence showing th at ST3 can modulate cancer progression.