Scientific article
OA Policy
English

Targeting PDGF-mediated recruitment of pericytes blocks vascular mimicry and tumor growth

Published inThe Journal of Pathology, vol. 246, no. 4, p. 447-458
Publication date2018
Abstract

Aggressive tumor cells can adopt an endothelial cell-like phenotype and contribute to the formation of a tumor vasculature, independent of tumor angiogenesis. This adoptive mechanism is referred to as vascular mimicry and it is associated with poor survival in cancer patients. To what extent tumor cells capable of vascular mimicry phenocopy the angiogenic cascade is still poorly explored. Here, we identify pericytes as important players in vascular mimicry. We found that pericytes are recruited by vascular mimicry-positive tumor cells in order to facilitate sprouting and to provide structural support of the vascular-like networks. The pericyte recruitment is mediated through platelet-derived growth factor (PDGF)-B. Consequently, preventing PDGF-B signaling by blocking the PDGF receptors with either the small tyrosine kinase inhibitor imatinib or blocking antibodies inhibits vascular mimicry and tumor growth. Collectively, the current study identifies an important role for pericytes in the formation of vascular-like structures by tumor cells. Moreover, the mechanism that controls the pericyte recruitment provides therapeutic opportunities for patients with aggressive vascular mimicry-positive cancer types. © 2018 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.

Keywords
  • Animals
  • Antineoplastic Agents, Immunological/pharmacology
  • Biological Mimicry/drug effects
  • Cell Communication/drug effects
  • Cell Line, Tumor
  • Cell Proliferation/drug effects
  • Coculture Techniques
  • Humans
  • Imatinib Mesylate/pharmacology
  • Melanoma, Experimental/blood supply/drug therapy/metabolism/pathology
  • Mice
  • Mice, Nude
  • Neovascularization, Pathologic
  • Pericytes/drug effects/metabolism/pathology
  • Platelet-Derived Growth Factor/antagonists & inhibitors/immunology/metabolism
  • Protein Kinase Inhibitors/pharmacology
  • Signal Transduction/drug effects
  • Time Factors
  • Tumor Burden/drug effects
  • Xenograft Model Antitumor Assays
Citation (ISO format)
THIJSSEN, Victor Ljl et al. Targeting PDGF-mediated recruitment of pericytes blocks vascular mimicry and tumor growth. In: The Journal of Pathology, 2018, vol. 246, n° 4, p. 447–458. doi: 10.1002/path.5152
Main files (1)
Article (Published version)
Identifiers
Journal ISSN0022-3417
208views
123downloads

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