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

Nolan, D. J., Ciarrocchi, A., Mellick, A. S., Jaggi, J. S., Bambino, K., Gupta, S., Heikamp, E., McDevitt, M. R., Scheinberg, D. A., Benezra, R., Mittal, V. (June 2007) Bone marrow-derived endothelial progenitor cells are a major determinant of nascent tumor neovascularization. Genes Dev, 21 (12). pp. 1546-58. ISSN 0890-9369 (Print)

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URL: https://www.ncbi.nlm.nih.gov/pubmed/17575055
DOI: 10.1101/gad.436307

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.

Item Type: Paper
Uncontrolled Keywords: Animals Cell Differentiation Cell Line, Tumor Endothelial Cells/ pathology Female Hematopoietic Stem Cells/ pathology Male Mammary Neoplasms, Experimental/blood supply/genetics/pathology Mice Mice, Inbred C57BL Mice, Transgenic Neoplasms, Experimental/ blood supply/genetics/ pathology Neovascularization, Pathologic Bone marrow transplantation tumor angiogenesis endothelial progenitor cells endothelial cells VE-cadherin neovascularization
Subjects: diseases & disorders > cancer > angiogenesis
diseases & disorders > cancer > cancer types > breast cancer
organs, tissues, organelles, cell types and functions > cell types and functions > cell types > endothelial progenitor cell
organs, tissues, organelles, cell types and functions > cell types and functions > cell types > endothelial progenitor cell
organs, tissues, organelles, cell types and functions > cell types and functions > cell types > endothelial progenitor cell
organs, tissues, organelles, cell types and functions > cell types and functions > cell types > progenitor cell > endothelial progenitor cell
organs, tissues, organelles, cell types and functions > cell types and functions > cell types > progenitor cell > endothelial progenitor cell
organs, tissues, organelles, cell types and functions > cell types and functions > cell types > progenitor cell > endothelial progenitor cell
CSHL Authors:
Communities: CSHL labs > Mittal lab
Depositing User: CSHL Librarian
Date: 15 June 2007
Date Deposited: 07 Nov 2011 19:26
Last Modified: 02 Apr 2018 19:57
PMCID: PMC1891431
Related URLs:
URI: http://repository.cshl.edu/id/eprint/23109

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