P-selectin-mediated platelet adhesion promotes tumor growth

Oncotarget. 2015 Mar 30;6(9):6584-96. doi: 10.18632/oncotarget.3164.

Abstract

Blood platelets foster carcinogenesis. We found that platelets are accumulated in human tumors. P-selectin deficiency and soluble P-selectin abolish platelet deposition within tumors, decreasing secretion of vascular endothelial growth factor and angiogenesis, thereby suppressing tumor growth. Binding of the P-selectin cytoplasmic tail to talin1 triggers the talin1 N-terminal head to interact with the β3 cytoplasmic tail. This activates αIIbβ3 and recruits platelets into tumors. Platelet infiltration into solid tumors occurs through a P-selectin-dependent mechanism.

Keywords: P-selectin; platelets; talin1; tumor growth; αIIbβ3.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blood Platelets / metabolism*
  • Cell Proliferation*
  • Female
  • Humans
  • Insulinoma / blood
  • Insulinoma / genetics
  • Insulinoma / metabolism*
  • Insulinoma / pathology
  • Melanoma, Experimental / blood
  • Melanoma, Experimental / metabolism*
  • Melanoma, Experimental / pathology
  • Mice, Inbred C57BL
  • Mice, Knockout
  • P-Selectin / blood
  • P-Selectin / genetics
  • P-Selectin / metabolism*
  • Pancreatic Neoplasms / blood
  • Pancreatic Neoplasms / genetics
  • Pancreatic Neoplasms / metabolism*
  • Pancreatic Neoplasms / pathology
  • Platelet Adhesiveness*
  • Platelet Glycoprotein GPIIb-IIIa Complex / metabolism
  • Protein Binding
  • Signal Transduction
  • Talin
  • Time Factors
  • Tumor Burden

Substances

  • P-Selectin
  • Platelet Glycoprotein GPIIb-IIIa Complex
  • SELP protein, human
  • Talin
  • Tln1 protein, mouse