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Chemotherapy Cytotoxicity of Human MCF-7 and MDA-MB 231 Breast Cancer Cells Is Altered by Osteoblast-Derived Growth Factors

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Abstract

One-third of women with breast cancer will develop bone metastases and eventually die from disease progression at these sites. Therefore, we analyzed the ability of human MG-63 osteoblast-like cells (MG-63 cells), MG-63 conditioned media (MG-63 CM), insulin-like growth factor I (IGF-I), and transforming growth factor beta 1 (TGF-β1) to alter the effects of adriamycin on cell cycle and apoptosis of estrogen receptor negative (ER−) MDA-MB-231 and 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 G2/M phase in the cell cycle and inhibited cell growth. In addition, adriamycin arrested the MCF-7 cells at G1/G0 phase and induced apoptosis of MDA-MB-231 cells. Exogenous IGF-I partially neutralized the adriamycin cytotoxicity/cytostasis of cancer cells. MG-63 CM and TGF-β1 partially neutralized the adriamycin cytotoxicity of MDA-MB-231 cells but enhanced adriamycin blockade of MCF-7 cells at G1/G0 phase. MG-63 osteoblast-like cells inhibited growth of MCF-7 cells while promoting growth and rescued MDA-MB-231 cells from adriamycin apoptosis in a collagen co-culture system. These data suggest that osteoblast-derived growth factors can 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.

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Acknowledgments

Michael Koutsilieris is a scholar affiliated with the Fonds de la Recherche en Sante du Quebec (FRSQ) and is currently supported by the Central Council of Health of Greece (KESY). Carlos Reyes-Moreno holds a fellowship award from the FRSQ and Dr. Antigone Sourla is the recipient of a research fellowship award from Endorecherche, Research Center, Laval University, Quebec, Canada. The authors thank Mr. Maurice Dufour for excellent technical assistance with flow cytometry.

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Authors and Affiliations

  1. Research Center, Centre Hospitalier Universitaire de Quebec (CHUQ), Laval University, Quebec City, Quebec, Canada

    Michael Koutsilieris M.D., Ph.D., Carlos Reyes-Moreno, Isabelle Choki, Antigone Sourla & Charles Doillon

  2. Department of Experimental Physiology, Medical School, University of Athens, 75 Micras Asias, Goudi, Athens, 117 27, Greece

    Michael Koutsilieris M.D., Ph.D.

  3. Endo/OncoResearch, Ltd., Athens, Greece

    Antigone Sourla

  4. Department of Medicine, Division of Oncology, Medical School, University of Ioannina, Ioannina, Greece

    Nicolas Pavlidis

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  1. Michael Koutsilieris M.D., Ph.D.
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  2. Carlos Reyes-Moreno
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  3. Isabelle Choki
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  4. Antigone Sourla
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  5. Charles Doillon
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Correspondence to Michael Koutsilieris M.D., Ph.D..

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Communicated by A. G. Papavassiliou

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Koutsilieris, M., Reyes-Moreno, C., Choki, I. et al. Chemotherapy Cytotoxicity of Human MCF-7 and MDA-MB 231 Breast Cancer Cells Is Altered by Osteoblast-Derived Growth Factors. Mol Med 5, 86–97 (1999). https://doi.org/10.1007/BF03402143

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