PDGFRβ+ perivascular progenitor cells in tumours regulate pericyte differentiation and vascular survival

Steven Song; Andrew J. Ewald; William Stallcup; Zena Werb; Gabriele Bergers

doi:10.1038/ncb1288

PDGFRβ⁺ perivascular progenitor cells in tumours regulate pericyte differentiation and vascular survival

Steven Song, Andrew J. Ewald, William Stallcup, Zena Werb, Gabriele Bergers

Research output: Contribution to journal › Article › peer-review

427 Scopus citations

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 PDGFRβ⁺ (platelet-derived growth factor receptor β) progenitor perivascular cells (PPCs) that have the ability to differentiate into pericytes and regulate vessel stability and vascular survival in tumours. A subset of PDGFRβ⁺ PPCs is recruited from bone marrow to perivascular sites in tumours. Specific inhibition of PDGFRβ signalling eliminates PDGFRβ⁺ PPCs and mature pericytes around tumour vessels, leading to vascular hyperdilation and endothelial cell apoptosis in pancreatic islet tumours of transgenic Rip1Tag2 mice.

Original language	English (US)
Pages (from-to)	870-879
Number of pages	10
Journal	Nature cell biology
Volume	7
Issue number	9
DOIs	https://doi.org/10.1038/ncb1288
State	Published - Sep 2005
Externally published	Yes

ASJC Scopus subject areas

Cell Biology

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10.1038/ncb1288

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@article{0af867fb9ee64d22a4f68a3dc0c9ca84,

title = "PDGFRβ+ perivascular progenitor cells in tumours regulate pericyte differentiation and vascular survival",

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 PDGFRβ+ (platelet-derived growth factor receptor β) progenitor perivascular cells (PPCs) that have the ability to differentiate into pericytes and regulate vessel stability and vascular survival in tumours. A subset of PDGFRβ+ PPCs is recruited from bone marrow to perivascular sites in tumours. Specific inhibition of PDGFRβ signalling eliminates PDGFRβ+ PPCs and mature pericytes around tumour vessels, leading to vascular hyperdilation and endothelial cell apoptosis in pancreatic islet tumours of transgenic Rip1Tag2 mice.",

author = "Steven Song and Ewald, {Andrew J.} and William Stallcup and Zena Werb and Gabriele Bergers",

note = "Funding Information: We thank N. Boudreau for valuable discussions and advice, D. Hanahan for RipTag2-Rag1ko/ko mice, N. Korets for excellent technical assistance, A. McMillan for statistical analysis, and S. Reynolds for help with the manuscript preparation. This work was supported by grants from the National Institutes of Health (R01 CA109390, R01 CA99948, RO1 CA95287, P01 CA72006), by an NIH Institutional NRSA fellowship to A.J.E. (5T32HL007731), by a grant from the American Cancer Society, and by start-up funds to G.B. from the Department of Neurological Surgery at UCSF.",

year = "2005",

month = sep,

doi = "10.1038/ncb1288",

language = "English (US)",

volume = "7",

pages = "870--879",

journal = "Nature cell biology",

issn = "1465-7392",

publisher = "Nature Publishing Group",

number = "9",

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T1 - PDGFRβ+ perivascular progenitor cells in tumours regulate pericyte differentiation and vascular survival

AU - Song, Steven

AU - Ewald, Andrew J.

AU - Stallcup, William

AU - Werb, Zena

AU - Bergers, Gabriele

N1 - Funding Information: We thank N. Boudreau for valuable discussions and advice, D. Hanahan for RipTag2-Rag1ko/ko mice, N. Korets for excellent technical assistance, A. McMillan for statistical analysis, and S. Reynolds for help with the manuscript preparation. This work was supported by grants from the National Institutes of Health (R01 CA109390, R01 CA99948, RO1 CA95287, P01 CA72006), by an NIH Institutional NRSA fellowship to A.J.E. (5T32HL007731), by a grant from the American Cancer Society, and by start-up funds to G.B. from the Department of Neurological Surgery at UCSF.

PY - 2005/9

Y1 - 2005/9

N2 - 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 PDGFRβ+ (platelet-derived growth factor receptor β) progenitor perivascular cells (PPCs) that have the ability to differentiate into pericytes and regulate vessel stability and vascular survival in tumours. A subset of PDGFRβ+ PPCs is recruited from bone marrow to perivascular sites in tumours. Specific inhibition of PDGFRβ signalling eliminates PDGFRβ+ PPCs and mature pericytes around tumour vessels, leading to vascular hyperdilation and endothelial cell apoptosis in pancreatic islet tumours of transgenic Rip1Tag2 mice.

AB - 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 PDGFRβ+ (platelet-derived growth factor receptor β) progenitor perivascular cells (PPCs) that have the ability to differentiate into pericytes and regulate vessel stability and vascular survival in tumours. A subset of PDGFRβ+ PPCs is recruited from bone marrow to perivascular sites in tumours. Specific inhibition of PDGFRβ signalling eliminates PDGFRβ+ PPCs and mature pericytes around tumour vessels, leading to vascular hyperdilation and endothelial cell apoptosis in pancreatic islet tumours of transgenic Rip1Tag2 mice.

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JO - Nature cell biology

JF - Nature cell biology

IS - 9

ER -

PDGFRβ⁺ perivascular progenitor cells in tumours regulate pericyte differentiation and vascular survival

Abstract

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