Pericytes Limit Tumor Cell Metastasis

J Clin Invest. 2006 Mar;116(3):642-51. doi: 10.1172/JCI25705. Epub 2006 Feb 9.

Abstract

Previously we observed that neural cell adhesion molecule (NCAM) deficiency in beta tumor cells facilitates metastasis into distant organs and local lymph nodes. Here, we show that NCAM-deficient beta cell tumors grew leaky blood vessels with perturbed pericyte-endothelial cell-cell interactions and deficient perivascular deposition of ECM components. Conversely, tumor cell expression of NCAM in a fibrosarcoma model (T241) improved pericyte recruitment and increased perivascular deposition of ECM molecules. Together, these findings suggest that NCAM may limit tumor cell metastasis by stabilizing the microvessel wall. To directly address whether pericyte dysfunction increases the metastatic potential of solid tumors, we studied beta cell tumorigenesis in primary pericyte-deficient Pdgfb(ret/ret) mice. This resulted in beta tumor cell metastases in distant organs and local lymph nodes, demonstrating a role for pericytes in limiting tumor cell metastasis. These data support a new model for how tumor cells trigger metastasis by perturbing pericyte-endothelial cell-cell interactions.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenoma, Islet Cell / blood supply
  • Adenoma, Islet Cell / genetics
  • Adenoma, Islet Cell / metabolism
  • Adenoma, Islet Cell / pathology*
  • Animals
  • Cell Communication / genetics
  • Endothelium, Vascular / metabolism
  • Endothelium, Vascular / pathology
  • Fibrosarcoma / blood supply
  • Fibrosarcoma / genetics
  • Fibrosarcoma / metabolism
  • Fibrosarcoma / pathology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Neoplasm Metastasis / pathology*
  • Neoplasm Metastasis / prevention & control*
  • Neovascularization, Pathologic / metabolism
  • Neural Cell Adhesion Molecules / deficiency
  • Neural Cell Adhesion Molecules / genetics
  • Neural Cell Adhesion Molecules / physiology
  • Pancreatic Neoplasms / blood supply
  • Pancreatic Neoplasms / genetics
  • Pancreatic Neoplasms / metabolism
  • Pancreatic Neoplasms / pathology*
  • Pericytes / metabolism
  • Pericytes / physiology*

Substances

  • Neural Cell Adhesion Molecules