Bone marrow-derived endothelial progenitor cells are a major determinant of nascent tumor neovascularization

Daniel J. Nolan, Alessia Ciarrocchi, Albert S. Mellick, Jaspreet S. Jaggi, Kathryn Bambino, Sunita Gupta, Emily Heikamp, Michael R. McDevitt, David A. Scheinberg, Robert Benezra, Vivek Mittal

Research output: Contribution to journalArticlepeer-review

350 Scopus citations


Tumors build vessels by cooption of pre-existing vasculature and de novo recruitment of bone marrow (BM)-derived endothelial progenitor cells (EPCs). However, the contribution and the functional role of EPCs in tumor neoangiogenesis are controversial. Therefore, by using genetically marked BM progenitor cells, we demonstrate the precise spatial and temporal contribution of EPCs to the neovascularization of three transplanted and one spontaneous breast tumor in vivo using high-resolution microscopy and flow cytometry. We show that early tumors recruit BM-derived EPCs that differentiate into mature BM-derived endothelial cells (ECs) and luminally incorporate into a subset of sprouting tumor neovessels. Notably, in later tumors, these BM-derived vessels are diluted with non-BM-derived vessels from the periphery, which accounts for purported differences in previously published reports. Furthermore, we show that specific ablation of BM-derived EPCs with α-particle-emitting anti-VE-cadherin antibody markedly impaired tumor growth associated with reduced vascularization. Our results demonstrate that BM-derived EPCs are critical components of the earliest phases of tumor neoangiogenesis.

Original languageEnglish (US)
Pages (from-to)1546-1558
Number of pages13
JournalGenes and Development
Issue number12
StatePublished - Jun 15 2007


  • Bone marrow transplantation
  • Endothelial cells
  • Endothelial progenitor cells
  • Neovascularization
  • Tumor angiogenesis
  • VE-cadherin

ASJC Scopus subject areas

  • Genetics
  • Developmental Biology


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