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Blood. 2010 Oct 28;116(17):3367-71. doi: 10.1182/blood-2010-02-271122. Epub 2010 May 7.

Bone marrow is a reservoir for proangiogenic myelomonocytic cells but not endothelial cells in spontaneous tumors.

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1
Department of Surgery, Harvard Medical School and Children’s Hospital Boston, 300 Longwood Ave., Boston, MA 02115, USA. andrew.dudley@childrens.harvard.edu

Abstract

The hypothesis that bone marrow-derived, circulating endothelial cells incorporate into tumor blood vessels is unresolved. We have measured the numbers of bone marrow-derived versus resident endothelial cells in spontaneous prostate cancers during different stages of tumor progression and in age-matched normal prostates. Bone marrow-derived endothelial cells were rare in dysplasia and in well differentiated cancers representing between 0 and 0.04% of the total tumor mass. Instead, approximately 99% of all tumor-associated bone marrow-derived cells were CD45(+) hematopoietic cells, including GR-1(+), F4-80(+), and CD11b(+) myeloid cells. Similar to peripheral blood mononuclear cells, these tumor-associated myeloid cells expressed matrix metalloproteinases (MMPs), consistent with their proposed catalytic role during tumor angiogenesis. Furthermore, freshly isolated CD11b(+) cells stimulated tumor endothelial cell cord formation by 10-fold in an in vitro angiogenesis assay. The bone marrow is, therefore, a reservoir for cells that augment tumor angiogenesis, but the tumor endothelium is derived primarily from the local environment.

PMID:
20453162
PMCID:
PMC2995361
DOI:
10.1182/blood-2010-02-271122
[Indexed for MEDLINE]
Free PMC Article
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