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

18 Citations (Scopus)

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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Stem Cells
Neoplasms
Pericytes
Blood Vessels
Flow Cytometry
Bone Marrow
Pharmaceutical Preparations
Vascular Smooth Muscle
Cyclophosphamide
Smooth Muscle Myocytes
Electron Microscopy
Endothelial Cells
Color
Transplantation
Tissue Donors
Polymerase Chain Reaction
Messenger RNA
DNA

Keywords

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

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Circulating perivascular progenitors : A target of PDGFR inhibition. / Mancuso, Patrizia; Martin-Padura, Ines; Calleri, Angelica; Marighetti, Paola; Quarna, Jessica; Rabascio, Cristina; Braidotti, Paola; Bertolini, Francesco.

In: International Journal of Cancer, Vol. 129, No. 6, 15.09.2011, p. 1344-1350.

Research output: Contribution to journalArticle

Mancuso, Patrizia ; Martin-Padura, Ines ; Calleri, Angelica ; Marighetti, Paola ; Quarna, Jessica ; Rabascio, Cristina ; Braidotti, Paola ; Bertolini, Francesco. / Circulating perivascular progenitors : A target of PDGFR inhibition. In: International Journal of Cancer. 2011 ; Vol. 129, No. 6. pp. 1344-1350.
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