Osteoblast-derived growth factors enhance adriamycin-cytostasis of MCF-7 human breast cancer cells

Bone only metastasis in patients with estrogen receptor (ER) positive breas t cancer reported to have favorable response to chemotherapy, favorable pro gnosis, and an "indolent" course. Therefore, we assessed the ability of MG- 63 osteoblast-like human osteosarcoma cells (MG-63 cells) and MG-63 conditi oned media (CM) to influence adriamycin-cytoxicity of ER-positive MCF-7 hum an breast cancer cells. Estradiol (E2; 100 nM) increased the distribution a t S and G2/M phases in the cell cycle and stimulated the growth of MCF-7 ce lls. Adriamycin (100 nM) inhibited the growth and arrested the MCF-7 cells supplemented with or without 100 nM of estradiol [(-E2) and (+E2) MCF-7 cul tures] at G2/M phase in the cell cycle. In addition, adriamycin (100 nM) in creased the distribution at G1/G0 phase in the cell cycle of (+E2) MCF-7 cu ltures. Adriamycin (100 nM and 10 mu M) did not induce apoptosis of MCF-7 c ells as assessed by flow cytometry and analysis of DNA fragmentation on sim ple agarose gel. Exogenous insulinlike growth factor I (IGF I) stimulated w hile transforming growth factor beta I (TGF beta 1) and MG-63 CM inhibited the growth of MCF-7 cells. Furthermore, MG-63 CM and TGF beta 1 enhanced wh ile exogenous IGF I reversed adriamycin (100 nM)-cytostasis of MCF-7 cells. These data suggested that osteoblastic CM contained growth factors, such a s TGF beta 1 capable of enhancing adriamycin-cytostasis, in vitro. Conceiva bly, these osteoblast-derived "enhancers" of chemotherapy-cytostasis can ex plain the favorable prognosis and "indolent" course of ER-positive breast c ancer patients with bone only metastasis.