1. Expansion of myeloid immune suppressor Gr+CD11b+ cells in tumor-bearing host directly promotes tumor angiogenesis.
- Author
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Yang L, DeBusk LM, Fukuda K, Fingleton B, Green-Jarvis B, Shyr Y, Matrisian LM, Carbone DP, and Lin PC
- Subjects
- Animals, Apoptosis, Bone Marrow metabolism, CD11b Antigen immunology, Cell Differentiation, Cells, Cultured, Disease Progression, Endothelium metabolism, Endothelium pathology, Female, Humans, Matrix Metalloproteinase 9 biosynthesis, Matrix Metalloproteinase 9 metabolism, Mice, Mice, Knockout, Necrosis, Neoplasm Transplantation, Neoplasms metabolism, Neoplasms pathology, Stem Cell Factor metabolism, Vascular Endothelial Growth Factor A metabolism, CD11b Antigen metabolism, Neoplasms blood supply, Neoplasms immunology, Neovascularization, Pathologic
- Abstract
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.
- Published
- 2004
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