P-selectin-mediated platelet adhesion promotes the metastasis of murine melanoma cells

PLoS One. 2014 Mar 14;9(3):e91320. doi: 10.1371/journal.pone.0091320. eCollection 2014.

Abstract

Studies have indicated that the aggregation of activated platelets with cancer cells facilitates tumor metastasis; the adhesion molecule P-selectin may be an important mediator of this process, but the detailed mechanism is unclear. In the current study, we established a B16F10 (B16) cell metastatic model in P-selectin knockout (P-sel-/-) mice to determine the effect of P-selectin-mediated platelet adhesion on metastasis. Compared with C57 mice, P-sel-/- mice developed fewer metastatic foci, and cell proliferation within the metastatic tumors was inhibited by P-selectin deficiency. The platelet refusion assay demonstrated that mice with P-sel-/- platelets developed fewer lung metastatic foci (P<0.01) with a lower microvascular density (MVD) than mice with wild-type platelets. A co-culture model of platelets and B16 cells was utilized to determine the difference in VEGF concentration in the supernatants. The results demonstrated that the supernatant from the P-sel-/- platelet/B16 co-culture had a lower concentration of VEGF. Therefore, our findings indicated that P-selectin deficiency inhibited the metastasis of B16 cells and that wild-type platelet refusion reversed this inhibition. The P-selectin-mediated interaction between platelets and B16 cells promoted angiogenesis by up-regulating VEGF.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Proliferation
  • Disease Models, Animal
  • Melanoma, Experimental / genetics
  • Melanoma, Experimental / metabolism*
  • Melanoma, Experimental / pathology*
  • Mice
  • Mice, Knockout
  • Neoplasm Metastasis
  • Neovascularization, Pathologic / genetics
  • Neovascularization, Pathologic / metabolism
  • P-Selectin / genetics
  • P-Selectin / metabolism*
  • Platelet Adhesiveness* / genetics
  • Vascular Endothelial Growth Factor A / genetics
  • Vascular Endothelial Growth Factor A / metabolism

Substances

  • P-Selectin
  • Vascular Endothelial Growth Factor A

Grants and funding

This work was supported by grants from Ministry of Science and Technology of China (National Basic Research Program of China 2010CB529702 to L.-J.W.), National Science Foundation of China (31271455 to L.-J.W.). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.