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Pericytes limit tumor cell metastasis.

Författare:
Publiceringsår: 2006
Språk: Engelska
Sidor: 642-651
Publikation/Tidskrift/Serie: J Clin Invest
Volym: 116
Nummer: 3
Dokumenttyp: Artikel
Förlag: American Society for Clinical Investigation

Sammanfattning

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.

Disputation

Nyckelord

  • Medicine and Health Sciences

Övriga

Published
Yes
  • ISSN: 0021-9738

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