I. Choki et al., Osteoblast-derived growth factors enhance adriamycin-cytostasis of MCF-7 human breast cancer cells, ANTICANC R, 18(6A), 1998, pp. 4213-4224
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.