RETINOIC ACID INHIBITS CELL-GROWTH IN HPV NEGATIVE CERVICAL-CARCINOMACELLS BY INDUCTION OF INSULIN-LIKE-GROWTH-FACTOR BINDING PROTEIN-5 (IGFBP-5) SECRETION

Retinoids have been demonstrated to inhibit epithelial cell growth and differentiation. We examined the anti-proliferative effects of retino ic acid (RA) in an HPV positive and negative cervical carcinoma cell l ine. Our findings indicate that EPV-negative C33A cervical carcinoma c ells are more sensitive to the growth inhibitory activity of retinoic acid (RA) than are HPV-positive CaSki cervical carcinoma cells. Howeve r, conditioned medium hows RA-treated C33A cells displayed strong grow th inhibitory activity in both C33A and CaSki cells. Since RA has been shown to modulate the expression of insulin-like growth factor bindin g proteins (IGFHPs) in many cells, we examined RA regulated expression of IGFBPs in medium isolated from RA treated C33A cells, IGFBP-5 was detectable in medium from C33A cells exposed to WA, and addition of pu rified exogenous IGFBP-5 resulted in growth inhibition of C33A cells. These results indicate that RA exerts it's anti-neoplastic effect in H PV negative cervical carcinoma cells via the overproduction of IGFBP-5 . (C) 1997 Academic Press.