Pericytes limit tumor cell metastasis.

Forskningsoutput: TidskriftsbidragArtikel i vetenskaplig tidskrift

Abstract

Previously we observed that neural cell adhesion molecule (NCAM) deficiency in P tumor cells facilitates metastasis into distant organs and local lymph nodes. Here, we show that NCAM-deficient P 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 P 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.

Detaljer

Författare
  • Xiaojie Xian
  • Joakim Hakansson
  • Anders Ståhlberg
  • Per Lindblom
  • Christer Betsholtz
  • Holger Gerhardt
  • Henrik Semb
Enheter & grupper
Forskningsområden

Ämnesklassifikation (UKÄ) – OBLIGATORISK

  • Cell- och molekylärbiologi
Originalspråkengelska
Sidor (från-till)642-651
TidskriftJournal of Clinical Investigation
Volym116
Utgivningsnummer3
StatusPublished - 2006
PublikationskategoriForskning
Peer review utfördJa