INVESTIGADORES
GIULIANELLI Sebastian Jesus
artículos
Título:
CARCINOMA-ASSOCIATED FIBROBLASTS ACTIVATE PROGESTERONE RECEPTORS AND INDUCE HORMONE INDEPENDENT MAMMARY TUMOR GROWTH: A ROLE FOR THE FGF-2/FGFR-2 AXIS
Autor/es:
SEBASTIÁN GIULIANELLI; JUAN P. CERLIANI; CAROLINE A. LAMB; VICTORIA T. FABRIS; MARÍA C. BOTTINO; MARÍA A. GOROSTIAGA; VIRGINIA NOVARO; ADRIÁN GÓNGORA; ALBERTO BALDI; ALFREDO MOLINOLO; CLAUDIA LANARI
Revista:
INTERNATIONAL JOURNAL OF CANCER. JOURNAL INTERNATIONAL DU CANCER.
Editorial:
JOHN WILEY & SONS INC
Referencias:
Año: 2008 vol. 123 p. 2518 - 2531
ISSN:
0020-7136
Resumen:
The mechanisms by which mammary carcinomas acquire hormone independence are still unknown. To study the role of cancer-associated fibroblasts (CAF) in the acquisition of hormone independence we used a hormone-dependent (HD) mouse mammary tumor and its hormone-independent (HI) variant, which grows in vivo without hormone supply. HI tumors express higher levels of FGFR-2 than HD tumors. In spite of their in vivo differences, both tumors have the same hormone requirement in primary cultures. We demonstrated that CAF from HI tumors (CAF-HI) growing in vitro, express higher levels of FGF-2 than HD counterparts (CAF-HD). FGF-2 activated the progesterone receptors (PR) in the tumor cells, thus increasing cell proliferation in both HI and HD tumors. CAF-HI induced a higher proliferative rate on the tumor cells and in PR activation than CAF-HD. The blockage of FGF-2 in the co-cultures or the genetic or pharmacological inhibition of FGFR-2 inhibited PR activation and tumor cell proliferation. Moreover, in vivo, the FGFR inhibitor decreased C4-HI tumor growth, whereas FGF-2 was able to stimulate C4-HD tumor growth as MPA. T47D human breast cancer cells were also stimulated by progestins, FGF-2 or CAF-HI, and this stimulation was abrogated by antiprogestins, suggesting that the murine C4-HI cells respond as the human T47D cells. In summary, this is the first study reporting differences between CAF from HD and HI tumors suggesting that CAF-HI actively participate in driving HI tumor growth.