title: Bone marrow is a reservoir for proangiogenic myelomonocytic cells but not endothelial cells in spontaneous tumors.
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.
authors.affiliation: Department of Surgery, Harvard Medical School and Children’s Hospital Boston, 300 Longwood Ave., Boston, MA 02115, USA. andrew.dudley@childrens.harvard.edu
authors.forename: Andrew C
authors.initials: AC
authors.lastname: Dudley
authors.forename: Taturo
authors.initials: T
authors.lastname: Udagawa
authors.forename: Juan M
authors.initials: JM
authors.lastname: Melero-Martin
authors.forename: Shou-Ching
authors.initials: SC
authors.lastname: Shih
authors.forename: Adam
authors.initials: A
authors.lastname: Curatolo
authors.forename: Marsha A
authors.initials: MA
authors.lastname: Moses
authors.forename: Michael
authors.initials: M
authors.lastname: Klagsbrun
mesh_terms: 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*
chemical_list: D017493:Leukocyte Common Antigens
references.citation: Cancer Cell. 2008 Mar;13(3):193-205
references.pmid: 18328424
references.citation: Nat Med. 2005 Mar;11(3):261-2
references.pmid: 15723071
references.citation: J Pathol. 2006 May;209(1):67-77
references.pmid: 16482496
references.citation: Blood. 2009 Nov 12;114(20):4583-91
references.pmid: 19779041
references.citation: Cancer Cell. 2008 Sep 9;14(3):201-11
references.pmid: 18772110
references.citation: Lab Invest. 2007 Sep;87(9):858-70
references.pmid: 17607298
references.citation: Proc Natl Acad Sci U S A. 2008 Aug 26;105(34):E54; author reply E55
references.pmid: 18715995
references.citation: Nat Rev Cancer. 2010 Feb;10(2):138-46
references.pmid: 20094048
references.citation: Biochim Biophys Acta. 2009 Aug;1796(1):50-4
references.pmid: 19393290
references.citation: Proc Natl Acad Sci U S A. 2006 Aug 15;103(33):12493-8
references.pmid: 16891410
references.citation: Int J Cancer. 2009 Oct 15;125(8):1771-7
references.pmid: 19582874
references.citation: Curr Opin Hematol. 2009 Jul;16(4):269-73
references.pmid: 19417649
references.citation: Blood. 2009 Jul 23;114(4):901-14
references.pmid: 19383967
references.citation: Proc Natl Acad Sci U S A. 2005 Dec 13;102(50):18111-6
references.pmid: 16326806
references.citation: PLoS One. 2009 Sep 17;4(9):e7067
references.pmid: 19759906
references.citation: Cancer Res. 2004 Sep 1;64(17):6137-43
references.pmid: 15342397
references.citation: Proc Natl Acad Sci U S A. 2008 May 6;105(18):6620-5
references.pmid: 18443294
references.citation: Cancer Cell. 2005 Sep;8(3):211-26
references.pmid: 16169466
references.citation: J Thromb Haemost. 2009 Jul;7 Suppl 1:49-52
references.pmid: 19630767
references.citation: Nat Med. 2001 Nov;7(11):1194-201
references.pmid: 11689883
references.citation: Prostate. 2003 May 15;55(3):219-37
references.pmid: 12692788
references.citation: Cancer Cell. 2004 Oct;6(4):409-21
references.pmid: 15488763
references.citation: Blood. 2007 Mar 1;109(5):1801-9
references.pmid: 17053059
references.citation: Am J Pathol. 2010 Apr;176(4):1564-76
references.pmid: 20167863