Abstract
The microvasculature consists of endothelial cells and their surrounding pericytes. Few studies on the regulatory mechanisms of tumour angiogenesis have focused on pericytes. Here we report the identification of tumour-derived PDGFRbeta (+) (platelet-derived growth factor receptor beta) progenitor perivascular cells (PPCs) that have the ability to differentiate into pericytes and regulate vessel stability and vascular survival in tumours. A subset of PDGFRbeta (+) PPCs is recruited from bone marrow to perivascular sites in tumours. Specific inhibition of PDGFRbeta signalling eliminates PDGFRbeta (+) PPCs and mature pericytes around tumour vessels, leading to vascular hyperdilation and endothelial cell apoptosis in pancreatic islet tumours of transgenic Rip1Tag2 mice.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Apoptosis / physiology
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Blood Vessels / growth & development*
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Blood Vessels / metabolism
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Blood Vessels / physiopathology
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Bone Marrow Cells / cytology
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Bone Marrow Cells / metabolism
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Cell Communication / physiology
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Cell Differentiation / physiology
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Cell Movement / physiology
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Cell Survival / physiology
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Coculture Techniques
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Endothelial Cells / physiology
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Female
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Insulinoma / blood supply
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Insulinoma / metabolism
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Insulinoma / physiopathology
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Male
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Mice
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Mice, Transgenic
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Neoplasms / blood supply*
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Neoplasms / metabolism
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Neoplasms / physiopathology
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Neovascularization, Pathologic / metabolism*
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Neovascularization, Pathologic / physiopathology
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Pancreatic Neoplasms / blood supply
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Pancreatic Neoplasms / metabolism
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Pancreatic Neoplasms / physiopathology
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Pericytes / cytology
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Pericytes / metabolism*
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Receptor, Platelet-Derived Growth Factor beta / metabolism*
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Stem Cells / cytology
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Stem Cells / metabolism*
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Tumor Cells, Cultured
Substances
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Receptor, Platelet-Derived Growth Factor beta