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PMID: 18328424 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Matrix metalloproteinase-9 is required for tumor vasculogenesis but not for angiogenesis: role of bone marrow-derived myelomonocytic cells.

Cancer cell ·Vol. 13 ·No. 3 ·2008-03-00 ·Pages 193-205

Ahn GO, Brown JM

Abstract

Tumor vasculature is derived from sprouting of local vessels (angiogenesis) and bone marrow (BM)-derived circulating cells (vasculogenesis). By using a model system of transplanting tumors into an irradiated normal tissue to prevent angiogenesis, we found that tumors were unable to grow in matrix metalloproteinase-9 (MMP-9) knockout mice, but tumor growth could be restored by transplantation of wild-type BM. Endothelial progenitor cells did not contribute significantly to this process. Rather, CD11b-positive myelomonocytic cells from the transplanted BM were responsible for tumor growth and the development of immature blood vessels in MMP-9 knockout mice receiving wild-type BM. Our results suggest that MMP-9 could be an important target for adjunct therapy to enhance the response of tumors to radiotherapy.

MeSH Terms
Animals Antineoplastic Agents/pharmacology,therapeutic use Bone Marrow Cells/drug effects,enzymology,immunology Bone Marrow Transplantation CD11b Antigen/metabolism Diphosphonates/pharmacology,therapeutic use Endothelial Cells/enzymology Imidazoles/pharmacology,therapeutic use Matrix Metalloproteinase 9/deficiency,genetics,metabolism Matrix Metalloproteinase Inhibitors Melanoma, Experimental Mice Mice, Inbred C3H Mice, Inbred C57BL Mice, Knockout Monocytes/drug effects,enzymology,immunology,transplantation Myeloid Cells/drug effects,enzymology,immunology,transplantation Neoplasms, Experimental/blood supply,drug therapy,enzymology,pathology,radiotherapy Neovascularization, Pathologic/enzymology,pathology,prevention & control Protease Inhibitors/pharmacology,therapeutic use Signal Transduction Stem Cells/enzymology Subcutaneous Tissue/blood supply,radiation effects,surgery Time Factors Zoledronic Acid
Chemicals
Antineoplastic Agents CD11b Antigen Diphosphonates Imidazoles Matrix Metalloproteinase Inhibitors Protease Inhibitors Zoledronic Acid Matrix Metalloproteinase 9 Mmp9 protein, mouse
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Ahn G-One
Division of Radiation and Cancer Biology, Department of Radiation Oncology, Stanford University School of Medicine, 269 Campus Drive, CCSR-South, Room 1255, Stanford, CA 94305, USA.
Brown J Martin
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Article Info
Journal
Cancer cell
Abbr.
Cancer Cell
ISSN
1878-3686
DOI
10.1016/j.ccr.2007.11.032
Published
2008-03-00
Pages
193-205
Language
English
Region
United States
NLM ID
101130617
PMCID
PMC2967441
Subset
IM
Grants
NCI NIH HHS · R01 CA118202 · United States
NCI NIH HHS · R01 CA118202-02 · United States
NCI NIH HHS · T32 CA009151 · United States
NCI NIH HHS · R01 CA-118202 · United States
Corrections
CommentIn
PMID: 18328420
External Links
PubMed source DOI: 10.1016/j.ccr.2007.11.032 PMC Full Text View journal details
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