Expansion of myeloid immune suppressor Gr+CD11b+ cells in tumor-bearing host directly promotes tumor angiogenesis.
We demonstrate a novel tumor-promoting role of myeloid immune suppressor Gr+CD11b+ cells, which are evident in cancer patients and tumor-bearing animals. These cells constitute approximately 5% of total cells in tumors. Tumors coinjected with Gr+CD11b+ cells exhibited increased vascular density, vascular maturation, and decreased necrosis. These immune cells produce high levels of MMP9. Deletion of MMP9 in these cells completely abolishes their tumor-promoting ability. Gr+CD11b+ cells were also found to directly incorporate into tumor endothelium. Consistent with this observation, Gr+CD11b+ cells acquire endothelial cell (EC) properties in tumor microenvironment and proangiogenic culture conditions. Our data provide evidence that Gr+CD11b+ cells of immune origin induced by tumors directly contribute to tumor growth and vascularization by producing MMP9 and differentiating into ECs.
Department of Cancer Biology, Vanderbilt University School of Medicine, Nashville, TN 37232, USA.
Li
L
Yang
Laura M
LM
DeBusk
Koari
K
Fukuda
Barbara
B
Fingleton
Brenda
B
Green-Jarvis
Yu
Y
Shyr
Lynn M
LM
Matrisian
David P
DP
Carbone
P Charles
PC
Lin
D000818:Animals; D017209:Apoptosis; D001853:Bone Marrow / Q000378:metabolism; D039481:CD11b Antigen / Q000276:immunology / Q000378:metabolism*; D002454:Cell Differentiation; D002478:Cells, Cultured; D018450:Disease Progression; D004727:Endothelium / Q000378:metabolism / Q000473:pathology; D005260:Female; D006801:Humans; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D009336:Necrosis; D009368:Neoplasm Transplantation; D009369:Neoplasms / Q000098:blood supply* / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D009389:Neovascularization, Pathologic; D019089:Stem Cell Factor / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
D039481:CD11b Antigen; D019089:Stem Cell Factor; D042461:Vascular Endothelial Growth Factor A; D020780:Matrix Metalloproteinase 9