Osteoblast-derived growth factors enhance adriamycin-cytostasis of MCF-7 human breast cancer cells.
Bone only metastasis in patients with estrogen receptor (ER) positive breast cancer reported to have favorable response to chemotherapy, favorable prognosis, and an "indolent" course. Therefore, we assessed the ability of MG-63 osteoblast-like human osteosarcoma cells (MG-63 cells) and MG-63 conditioned media (CM) to influence adriamycin-cytotoxicity of ER-positive MCF-7 human breast cancer cells. Estradiol (E2; 100 nM) increased the distribution at S and G2/M phases in the cell cycle and stimulated the growth of MCF-7 cells. 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 cultures] at G2/M phase in the cell cycle. In addition, adriamycin (100 nM) increased the distribution at G1/G0 phase in the cell cycle of (+E2) MCF-7 cultures. Adriamycin (100 nM and 10 microM) did not induce apoptosis of MCF-7 cells as assessed by flow cytometry and analysis of DNA fragmentation on simple agarose gel. Exogenous insulin-like growth factor I (IGF I) stimulated while transforming growth factor beta 1 (TGF beta 1) and MG-63 CM inhibited the growth of MCF-7 cells. Furthermore, MG-63 CM and TGF beta 1 enhanced while exogenous IGF I reversed adriamycin (100 nM)-cytostasis of MCF-7 cells. These data suggested that osteoblastic CM contained growth factors, such as TGF beta 1 capable of enhancing adriamycin-cytostasis, in vitro. Conceivably, these osteoblast-derived "enhancers" of chemotherapy-cytostasis can explain the favorable prognosis and "indolent" course of ER-positive breast cancer patients with bone only metastasis.
Choki
I
I
Molecular Endocrinology Laboratory, Pavillon C.H.U.L-C.H.U.Q, Laval University, Ste. Foy, Quebec, Canada.
Sourla
A
A
Reyes-Moreno
C
C
Koutsilieris
M
M
D000970:Antineoplastic Agents / Q000633:toxicity*; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D001859:Bone Neoplasms; D001943:Breast Neoplasms; D002453:Cell Cycle / Q000187:drug effects* / Q000502:physiology; D002455:Cell Division / Q000187:drug effects*; D017077:Culture Media, Conditioned; D053938:DNA Fragmentation / Q000187:drug effects; D004317:Doxorubicin / Q000633:toxicity*; D004357:Drug Synergism; D004958:Estradiol / Q000494:pharmacology; D005260:Female; D016195:G2 Phase; D006133:Growth Substances / Q000494:pharmacology / Q000502:physiology*; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology / Q000502:physiology; D008938:Mitosis; D010006:Osteoblasts / Q000502:physiology*; D012516:Osteosarcoma; D016212:Transforming Growth Factor beta / Q000494:pharmacology / Q000502:physiology; D014407:Tumor Cells, Cultured; D014410:Tumor Stem Cell Assay
D000970:Antineoplastic Agents; D017077:Culture Media, Conditioned; D006133:Growth Substances; D016212:Transforming Growth Factor beta; D004958:Estradiol; D007334:Insulin-Like Growth Factor I; D004317:Doxorubicin