title: Morphine decreases the pro-angiogenic interaction between breast cancer cells and macrophages in vitro.
abstract: Interactions between the various cell types that constitute a solid tumour are essential to the biology of the tumour. We evaluated the effect of morphine on the proangiogenic interaction taking place between macrophages and breast cancer cells in vitro. The conditioned medium (CM) from breast cancer cells co-cultured with macrophages elicited endothelial cell proliferation and tube formation. This effect was inhibited if the co-culture occurred in the presence of morphine. The CM from breast cancer cells or macrophages grown individually, whether or not prepared in the presence of morphine, was ineffective in stimulating EC proliferation or tube formation. Using a mouse antibody array, we identified several angiogenesis-regulating factors differentially expressed in the CM of co-cultured cells prepared in the presence or absence of morphine, amongst which interleukin (IL)-6, tumour necrosis factor (TNF)-α and vascular endothelial growth factor (VEGF)-A. VEGF was induced in both cell types by the co-culture and this was prevented by morphine in a non-naloxone reversible fashion. The effect of CM from co-cultured cells on endothelial tube formation, but not proliferation, was prevented by anti-VEGF neutralizing antibody. Our results indicate that morphine prevents, in part via modulating VEGF-A expression, the pro-angiogenic interaction between macrophages and breast cancer cells.
authors: University of Queensland School of Pharmacy, PACE, 20 Cornwall Street. Woollloongabba QLD 4102, Australia.
authors: Samira
authors: S
authors: Khabbazi
authors: University of Queensland School of Pharmacy, PACE, 20 Cornwall Street. Woollloongabba QLD 4102, Australia.
authors: Zeyad D
authors: ZD
authors: Nassar
authors: CNRS UPR3212, Institut des Neurosciences Cellulaires et Intégratives, Centre National de la Recherche Scientifique and University of Strasbourg, 5 rue Blaise Pascal, 67084 Strasbourg, France.
authors: Yannick
authors: Y
authors: Goumon
authors: University of Queensland School of Pharmacy, PACE, 20 Cornwall Street. Woollloongabba QLD 4102, Australia.
authors: Marie-Odile
authors: MO
authors: Parat
mesh_terms: D000818:Animals; D002450:Cell Communication / Q000187:drug effects*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D018920:Coculture Techniques; D005260:Female; D008264:Macrophages / Q000378:metabolism* / Q000473:pathology; D015674:Mammary Neoplasms, Animal / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D009020:Morphine / Q000494:pharmacology*; D009389:Neovascularization, Pathologic / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D000067996:RAW 264.7 Cells
chemical_list: D009020:Morphine