Chemotherapy cytotoxicity of human MCF-7 and MDA-MB 231 breast cancer cells is altered by osteoblast-derived growth factors

One-third of women with breast cancer will develop bone metastases and even tually die from disease progression at these sites. Therefore, we analyzed the ability of human MG-63 osteoblast-like cells (MG-63 cells), MG-63 condi tioned media (MG-63 CM), insulin-like growth factor I (IGF-I), and transfor ming growth factor beta 1 (TGP-beta 1) to alter the effects of adriamycin o n cell cycle and apoptosis of estrogen receptor negative (ER-) MDA-MB-231 a nd positive (ER+) MCF-7 breast cancer cells, using cell count, trypan blue exclusion, flow cytometry, detection of DNA fragmentation by simple agarose gel,and the terminal deoxynucleotidyl transferase (TdT)-mediated nick end- labeling method for apoptosis (TUNEL assay). Adriamycin arrested MCF-7 and MDA-MB-231 cells at G(2)/M phase in the cell cycle and inhibited cell growt h. In addition, adriamycin arrested the MCF-7 cells at G(1)/G(0) phase and induced apoptosis of MDA-MB-231 cells. Exogenous IGF-I partially neutralize d the adriamycin cytotoxicity/cytostasis of cancer cells. MG-63 CM and TGF- beta 1 partially neutralized the adriamycin cytotoxicity of MDA-MB-231 cell s but enhanced adriamycin blockade of MCF-7 cells at G(1)/G(0) phase, MG-63 osteoblast-like cells inhibited growth of MCF-7 cells while promoting grow th and rescued MDA-MB-231 cells from adriamycin apoptosis in a collagen coc ulture system. These data suggest that osteoblast-derived growth factors ca n alter the chemotherapy response of breast cancer cells. Conceivably, host tissue (bone)-tumor cell interactions can modify the clinical response to chemotherapy in patients with advanced breast cancer.