Tumor-derived microvesicles modulate the establishment of metastatic melanoma in a phosphatidylserine-dependent

Luize G Lima1, Roger Chammas, Robson Q Monteiro

  • 1Division of Experimental Medicine, National Cancer Institute, RJ, Brazil; Institute of Medical Biochemistry, Federal University of Rio de Janeiro, RJ, Brazil. lglima@bioqmed.ufrj.br

Cancer Letters
|April 30, 2009
PubMed

Insights

Tumor microvesicles containing phosphatidylserine (PS) promote melanoma metastasis by suppressing immune responses. Annexin V reversed these pro-metastatic effects, highlighting PS

Area of Science:

  • Immunology
  • Oncology
  • Cell Biology

Background:

  • Phosphatidylserine (PS) exposure on microvesicles influences inflammatory responses in malignancy.
  • B16F10 melanoma cells generate abundant PS-containing microvesicles in vitro.

Purpose of the Study:

  • To investigate the role of PS-containing tumor microvesicles in melanoma metastasis.
  • To determine if these microvesicles can overcome host resistance to melanoma.

Main Methods:

  • In vitro analysis of PS-microvesicle production by B16F10 cells.
  • Assessment of microvesicle effects on macrophage TGF-beta(1) production.
  • In vivo studies of B16F10 cell metastasis in C57BL/6 and BALB/c mice, with and without annexin V treatment.

Main Results:

  • B16F10 microvesicles increased macrophage TGF-beta(1) production.
  • Microvesicles enhanced B16F10 cell metastasis in C57BL/6 mice.
  • Microvesicles induced metastasis in normally resistant BALB/c mice.
  • Annexin V reversed the pro-metastatic effects of microvesicles.

Conclusions:

  • Tumor-derived microvesicles promote melanoma metastasis in a PS-dependent manner.
  • These microvesicles may facilitate metastasis by down-regulating host anti-tumoral immunity.
  • This study provides the first evidence of microvesicles driving melanoma metastasis via PS signaling.