“Inoculated carcinoma associated fibroblasts and hormone independent tumor growth”

SAHORES, ANA; FABRIS, VICTORIA; VANZULLI, SILVIA; LANARI, CLAUDIA; LAMB, CAROLINE A.

Washington d.c., EEUU

Congreso; American Association for Cancer Research; 2010

Murine mammary carcinomas from the MPA-murine breast cancer model express estrogen and progesterone receptors and transit through different stages of hormone dependence. Hormone dependent (HD) tumors only grow in the presence of medroxyprogesterone acetate (MPA) and hormone independent (HI) variants are those that grow without hormone supply. In co-culture studies we have demonstrated that carcinoma associated fibroblasts (CAF) from HI tumors (CAF HI) can stimulate epithelial cell proliferation better than those from HD tumors (CAF HD). However, in vivo, CAF-HI inoculated together with purified epithelial cells (EPI) only increased tumor growth of EPI HI and they were not able to replace the hormone requirement of EPI HD. Thus, the aim of this study was to investigate the role of CAF HI enhancing HI tumor growth and to elucidate why CAF HI failed to stimulate HD cells in vivo. For this purpose murine C4-HI tumors were transplanted in BALB/c-wt (wt) or in BALB/c-GFP (GFP) mice. Mice were subcutaneously inoculated with EPI HI alone or co-mingled with CAF HI-wt (in GFP mice) or CAF HI-GFP (in wt mice) and the resulting tumors were excised at different time points. Fluorescence analysis of frozen sections indicated that inoculated CAF HI-GFP were detected 7 days after their inoculum in wt mice whereas they were no longer detected at later time points. To elucidate how are CAF HI able to enhance tumor growth when co-inoculated with EPI HI cells, we quantified polymorphonuclear (hematoxilin and eosin) and mast cells (toluidine blue staining) in the EPI HI + CAF HI group and in the EPI HI group and no significant differences were observed. In similar experiments when cells were inoculated intradermically to evaluate angiogenesis, and animals were sacrificed after different time points, we observed that on day 5, there was a significantly higher number of vessels in the co-inoculated group (Control 1.1±0.1; CAF HI 1.8± 0.8; EPI HI 2.0±0.7; EPI HI + CAF HI 3.3±0.5 p<0.05). In summary we conclude that the inoculated CAF fail to induce HD growth because they do not persist in the tumor mass although they may participate during the first stages of tumor growth favoring angiogenesis.