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.
Yang
Li
L
Department of Cancer Biology, Vanderbilt University School of Medicine, Nashville, TN 37232, USA.
DeBusk
Laura M
LM
Fukuda
Koari
K
Fingleton
Barbara
B
Green-Jarvis
Brenda
B
Shyr
Yu
Y
Matrisian
Lynn M
LM
Carbone
David P
DP
Lin
P Charles
PC
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