Tumor-derived Microvesicles Modulate the Establishment of Metastatic Melanoma in a Phosphatidylserine-Dependent Manner

Cancer Lett. 2009 Oct 8;283(2):168-75. doi: 10.1016/j.canlet.2009.03.041. Epub 2009 Apr 28.

Abstract

Exposure of phosphatidylserine (PS) on cellular membranes and membrane-derived microvesicles stimulates a number of anti-inflammatory responses involved in malignant processes. Herein we show that B16F10 cells, a highly metastatic melanoma cell line, produce large quantities of PS-containing microvesicles in vitro. Tumor microvesicles increased TGF-beta(1) production by cultured macrophages and, in vivo, enhanced the metastatic potential of B16F10 cells in C57BL/6 mice, both effects being reversed by annexin V. Most strikingly, microvesicles induced melanoma metastasis in BALB/c mice, which are normally resistant to this tumor cell line. Altogether, this is the first demonstration that tumor-derived microvesicles favor the establishment of melanoma metastasis in a PS-dependent manner, possibly by down-regulating the host's inflammatory and/or anti-tumoral immune responses.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Cell-Derived Microparticles / chemistry
  • Cell-Derived Microparticles / immunology*
  • Cell-Derived Microparticles / metabolism*
  • Flow Cytometry
  • Macrophages / immunology
  • Macrophages / metabolism
  • Melanoma, Experimental / immunology*
  • Melanoma, Experimental / metabolism*
  • Melanoma, Experimental / pathology
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Microscopy, Electron, Transmission
  • Microscopy, Fluorescence
  • Neoplasm Invasiveness / immunology
  • Phosphatidylserines / metabolism*
  • Transforming Growth Factor beta1 / immunology
  • Transforming Growth Factor beta1 / metabolism

Substances

  • Phosphatidylserines
  • Transforming Growth Factor beta1