Pericytes limit tumor cell metastasis.

• 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.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)

Nyckelord

Adenoma

Islet Cell

blood supply

genetics

metabolism

pathology

Animals

Cell Communication

genetics

Endothelium

Vascular

metabolism

pathology

Fibrosarcoma

blood supply

genetics

metabolism

pathology

Mice

Mice

Inbred C57BL

Mice

Knockout

Neoplasm Metastasis

pathology

prevention & control

Neovascularization

Pathologic

metabolism

Neural Cell Adhesion Molecules

deficiency

genetics

physiology

Pancreatic Neoplasms

blood supply

genetics

metabolism

pathology

Pericytes

metabolism

physiology

Publikations- och innehållstyp

ref (ämneskategori)

art (ämneskategori)