Circulating perivascular progenitors: A target of PDGFR inhibition

Patrizia Mancuso, Ines Martin-Padura, Angelica Calleri, Paola Marighetti, Jessica Quarna, Cristina Rabascio, Paola Braidotti, Francesco Bertolini

Research output: Contribution to journalArticle

Abstract

Cancer blood vessels consist of two interacting types of cells: inner lining endothelial cells (ECs) and surrounding perivascular cells (pericytes, vascular smooth muscle cells or mural cells). PDGFRbeta(CD140b)+ progenitor perivascular cells (PPC) can differentiate into pericytes and regulate vessel stability and vascular survival in tumors. Similarly to what we have done with circulating ECs and progenitors, we developed a flow cytometry procedure for the enumeration of circulating PPCs and the study of their viability in murine models of cancer and in cancer patients. DNA+CD45-CD31-CD140b+ cells were enumerated by six-colour flow cytometry, their morphology was studied by electron microscopy, PPC specificity confirmed by reverse trascription-PCR (RT-PCR) expression of CD140b mRNA, and viability assessed by Syto16 and 7AAD. In preclinical marrow transplantation studies, 9 ± 4% of circulating PPCs were derived from the marrow donor. PPCs were increased in cancer-bearing mice and in patients affected by some types of cancer. At variance with the kinetic of circulating endothelial progenitors, high-dose cyclophosphamide reduced the number of viable PPCs. The administration of sunitinib, a drug known to inhibit PDGFR, was associated in murine models and in cancer patients with an increase of apoptotic/necrotic circulating PPC, suggesting a direct targeting of these cells. PPC enumeration might be studied as a tool for the definition of the optimal biologic dose of anti-PDGFR drugs and investigated clinically as a possible predictive/prognostic tool in patients receiving anti-PDGFR drugs.

Original languageEnglish
Pages (from-to)1344-1350
Number of pages7
JournalInternational Journal of Cancer
Volume129
Issue number6
DOIs
Publication statusPublished - Sep 15 2011

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Keywords

  • angiogenesis
  • anti-PDGFR
  • antiangiogenic therapy
  • circulating perivascular progenitors
  • PDGFR

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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