Bone marrow-derived endothelial progenitor cells are a major determinant of nascent tumor neovascularization. Academic Article uri icon

Overview

abstract

  • 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 alpha-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.

publication date

  • June 15, 2007

Research

keywords

  • Endothelial Cells
  • Hematopoietic Stem Cells
  • Neoplasms, Experimental
  • Neovascularization, Pathologic

Identity

PubMed Central ID

  • PMC1891431

Scopus Document Identifier

  • 34250719709

PubMed ID

  • 17575055

Additional Document Info

volume

  • 21

issue

  • 12