Presence of intratumoral platelets is associated with tumor vessel structure and metastasis

BMC Cancer. 2014 Mar 10:14:167. doi: 10.1186/1471-2407-14-167.

Abstract

Background: Platelets play a fundamental role in maintaining hemostasis and have been shown to participate in hematogenous dissemination of tumor cells. Abundant platelets were detected in the tumor microenvironment outside of the blood vessel, thus, platelet -tumor cell interaction outside of the bloodstream may play a role in regulating primary tumor growth and metastasis initiation. However, it is unclear that platelet depletion affects tumor vessel structure and dynamics.

Methods: Using thrombocytopenia induction in two different tumor-bearing mouse models, tumor tissues were performed by Westernblotting and immunohistochemical staining. Vascular permeability was evaluated by determination of intratumoral Evans blue and Miles vascular permeability assay. Furthermore, microdialysis was used to examining the intratumoral extracellular angiogenic growth factors (VEGF, TGF-β) by ELISA.

Results: Platelet depletion showed no change in tumor growth and reduced lung metastasis. Platelet depletion led to reduced tumor hypoxia and Met receptor activation and was associated with a decreased release of MMP-2, 9, PAI-1, VEGF, and TGF-β. Tumor vessels in platelet-depleted mice showed impaired vessel density and maturation.

Conclusions: Our findings demonstrate that platelets within the primary tumor microenvironment play a critical role in the induction of vascular permeability and initiation of tumor metastasis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiogenesis Inducing Agents / metabolism
  • Animals
  • Blood Platelets / metabolism*
  • Blood Platelets / pathology
  • Blood Vessels / metabolism
  • Blood Vessels / pathology
  • Capillary Permeability
  • Disease Models, Animal
  • Hypoxia
  • Hypoxia-Inducible Factor 1, alpha Subunit / metabolism
  • Lung Neoplasms / secondary
  • Matrix Metalloproteinase 2 / metabolism
  • Matrix Metalloproteinase 9 / metabolism
  • Melanoma, Experimental
  • Mice
  • Neoplasm Metastasis
  • Neoplasms / metabolism*
  • Neoplasms / pathology*
  • Neovascularization, Pathologic*
  • Plasminogen Activator Inhibitor 1 / metabolism
  • Proto-Oncogene Proteins c-met / metabolism
  • Transforming Growth Factor beta1 / metabolism
  • Tumor Burden

Substances

  • Angiogenesis Inducing Agents
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • Plasminogen Activator Inhibitor 1
  • Transforming Growth Factor beta1
  • Proto-Oncogene Proteins c-met
  • Matrix Metalloproteinase 2
  • Matrix Metalloproteinase 9