Morphine decreases the pro-angiogenic interaction between breast cancer cells and macrophages in vitro

Sci Rep. 2016 Aug 12:6:31572. doi: 10.1038/srep31572.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Communication / drug effects*
  • Cell Line, Tumor
  • Cell Proliferation / drug effects*
  • Coculture Techniques
  • Female
  • Macrophages / metabolism*
  • Macrophages / pathology
  • Mammary Neoplasms, Animal / drug therapy
  • Mammary Neoplasms, Animal / metabolism*
  • Mammary Neoplasms, Animal / pathology
  • Mice
  • Morphine / pharmacology*
  • Neovascularization, Pathologic / drug therapy
  • Neovascularization, Pathologic / metabolism*
  • Neovascularization, Pathologic / pathology
  • RAW 264.7 Cells

Substances

  • Morphine