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Pericytes limit tumor cell metastasis

Item Type:Article
Title:Pericytes limit tumor cell metastasis
Creators Name:Xian, X., Håkansson, J., Ståhlberg, A., Lindblom, P., Betsholtz, C., Gerhardt, H. and Semb, H.
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.
Keywords:Cell Communication, Fibrosarcoma, Inbred C57BL Mice, Islet Cell Adenoma, Knockout Mice, Neoplasm Metastasis, Neural Cell Adhesion Molecules, Pancreatic Neoplasms, Pathologic Neovascularization, Pericytes, Vascular Endothelium, Animals, Mice
Source:Journal of Clinical Investigation
Publisher:American Society for Clinical Investigation
Page Range:642-651
Date:1 March 2006
Official Publication:https://doi.org/10.1172/JCI25705
PubMed:View item in PubMed

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