Bone marrow is a reservoir for proangiogenic myelomonocytic cells but not endothelial cells in spontaneous tumors.
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.
Dudley
Andrew C
AC
Department of Surgery, Harvard Medical School and Children’s Hospital Boston, 300 Longwood Ave., Boston, MA 02115, USA. andrew.dudley@childrens.harvard.edu
Udagawa
Taturo
T
Melero-Martin
Juan M
JM
Shih
Shou-Ching
SC
Curatolo
Adam
A
Moses
Marsha A
MA
Klagsbrun
Michael
M
D000230:Adenocarcinoma / Q000473:pathology*; D000818:Animals; D001853:Bone Marrow / Q000473:pathology*; D042783:Endothelial Cells / Q000473:pathology*; D006801:Humans; D017493:Leukocyte Common Antigens / Q000276:immunology; D008297:Male; D051379:Mice; D022423:Myeloid Cells / Q000276:immunology / Q000473:pathology*; D009389:Neovascularization, Pathologic / Q000473:pathology; D011467:Prostate / Q000166:cytology / Q000473:pathology; D011471:Prostatic Neoplasms / Q000473:pathology*
D017493:Leukocyte Common Antigens
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