Pericytes limit tumor cell metastasis.

TY - JOUR

T1 - Pericytes limit tumor cell metastasis.

AU - Xian, Xiaojie

AU - Håkansson, Joakim

AU - Ståhlberg, Anders

AU - Lindblom, Per

AU - Betsholtz, Christer

AU - Gerhardt, Holger

AU - Semb, Tor Henrik

N1 - Keywords: Adenoma, Islet Cell; Animals; Cell Communication; Endothelium, Vascular; Fibrosarcoma; Mice; Mice, Inbred C57BL; Mice, Knockout; Neoplasm Metastasis; Neovascularization, Pathologic; Neural Cell Adhesion Molecules; Pancreatic Neoplasms; Pericytes

PY - 2006

Y1 - 2006

N2 - 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.

AB - 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.

U2 - 10.1172/JCI25705

DO - 10.1172/JCI25705

M3 - Journal article

C2 - 16470244

SN - 0021-9738

VL - 116

SP - 642

EP - 651

JO - Journal of Clinical Investigation

JF - Journal of Clinical Investigation

IS - 3

ER -