Matrix metalloproteinase-9 is required for tumor vasculogenesis but not for angiogenesis: role of bone marrow-derived myelomonocytic cells.
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.
Ahn
G-One
GO
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
JM
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use; D001854:Bone Marrow Cells / Q000187:drug effects / Q000201:enzymology* / Q000276:immunology; D016026:Bone Marrow Transplantation; D039481:CD11b Antigen / Q000378:metabolism; D004164:Diphosphonates / Q000494:pharmacology / Q000627:therapeutic use; D042783:Endothelial Cells / Q000201:enzymology; D007093:Imidazoles / Q000494:pharmacology / Q000627:therapeutic use; D020780:Matrix Metalloproteinase 9 / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D061965:Matrix Metalloproteinase Inhibitors; D008546:Melanoma, Experimental; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009000:Monocytes / Q000187:drug effects / Q000201:enzymology* / Q000276:immunology / Q000637:transplantation; D022423:Myeloid Cells / Q000187:drug effects / Q000201:enzymology* / Q000276:immunology / Q000637:transplantation; D009374:Neoplasms, Experimental / Q000098:blood supply* / Q000188:drug therapy / Q000201:enzymology* / Q000473:pathology / Q000532:radiotherapy; D009389:Neovascularization, Pathologic / Q000201:enzymology* / Q000473:pathology / Q000517:prevention & control; D011480:Protease Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D015398:Signal Transduction; D013234:Stem Cells / Q000201:enzymology; D040521:Subcutaneous Tissue / Q000098:blood supply / Q000528:radiation effects / Q000601:surgery; D013997:Time Factors; D000077211:Zoledronic Acid
D000970:Antineoplastic Agents; D039481:CD11b Antigen; D004164:Diphosphonates; D007093:Imidazoles; D061965:Matrix Metalloproteinase Inhibitors; D011480:Protease Inhibitors; D000077211:Zoledronic Acid; D020780:Matrix Metalloproteinase 9; C501830:Mmp9 protein, mouse