GIULIANELLI Sebastian Jesus
congresos y reuniones científicas
STROMAL FIBROBLASTS FROM HORMONE-INDEPENDENT CARCINOMAS. BETTER EPITHELIAL GROWTH PARTNERS THAN THOSE FROM HORMONE-DEPENDENT TUMORS
SEBASTIÁN GIULIANELLI; CAROLINE A. LAMB; MARÍA CECILIA BOTTINO; JUAN PABLO CERLIANI; ROCÍO SOLDATI; MARÍA ALICIA GOROSTIAGA; VICTORIA FABRIS; SILVIA I.VANZULLI; ALFREDO MOLINOLO; CLAUDIA LANARI
Mount Holyoke College, South Hadley, MA. USA.
Conferencia; Gordon Conference on Hormone action in development and cancer; 2005
Progestin-independent (PI) medroxyprogesterone acetate- induced mouse mammary carcinomas grow in vivo without exogenous progestin supply, although they retain high levels of estrogen and progesterone receptors (PR) and regress after antiprogestin treatment. Interestingly, their purified epithelial cells, the malignant compartment, grow very slowly when cultured in vitro, unless they are co-cultured with stromal fibroblasts. To study a possible role of these fibroblasts in PI tumor growth we have performed co-cultures of epithelial tumor cells from both progestin-dependent (PD) and PI tumors, and stromal fibroblasts obtained from PD tumors or PI tumors. Using 1% charcoalized fetal calf serum cell growth was observed only in the co-culture dishes; no significant growth was seen in the individually seeded cell populations. PD and PI epithelial cell growth was significantly better stimulated in co-cultures with stromal fibroblasts from PI tumors as compared with those obtained from PD carcinomas (p<0.05), and this stimulatory effect was inhibited by antiprogestins (p<0.05). In mobility gel shifts assays designed to investigate whether fibroblasts were able to activate epithelial PR, PI-derived fibroblasts were more efficient than their PD counterpart to increase PR-DNA binding. Our results strongly suggest a fundamental role for stromal fibroblasts promoting hormone-independent tumor growth under the modulatory control of the progesterone receptor.