Abstract: |
Neoangiogenesis involves both bone marrow-derived myelomonocytic and endothelial progenitor cells as well as endothelial cells coopted from surrounding vessels. Cytokines induce these cells to proliferate, migrate, and exit the cell cycle to establish the vasculature; however, which cell cycle regulators play a role in these processes is largely unknown. Here, we report that mice lacking the cell cycle inhibitors p130 and p27 show defects in tumor neoangiogenesis, both in xenografts and spontaneously arising tumors. This defect is associated with impaired mobilization of endothelial and myelomonocytic angiogenic progenitors from the bone marrow. This article documents the role of these molecules in angiogenesis and further suggests that cell expansion and mobilization from the bone marrow of angiogenic precursors are separable events. © 2005 by The National Academy of Sciences of the USA. |
Keywords: |
controlled study; vascular endothelial growth factor a; unclassified drug; nonhuman; flow cytometry; protein function; cell proliferation; proteins; cell cycle protein; mouse; animal; cytology; metabolism; animals; cell cycle proteins; mice; animal tissue; bone marrow cells; cells, cultured; cell cycle; bone marrow; animal experiment; protein; tumor xenograft; pathology; cell line, tumor; vasculotropin receptor 2; angiogenesis; neovascularization, pathologic; vascular endothelial growth factor receptor-2; physiology; time; time factors; transgenic mouse; mice, transgenic; stem cell; endothelium cell; biosynthesis; cell culture; drug combination; vascular endothelium; endothelium, vascular; cyclin dependent kinase inhibitor 1b; cd11b antigen; cyclin-dependent kinase inhibitor p27; tumor suppressor proteins; tumor cell line; vasculotropin a; collagen; cell migration; cyclin-dependent kinase inhibitors; bone marrow cell; matrigel; neoplasm transplantation; drug combinations; tumor suppressor protein; vascular endothelial growth factor receptor-1; tumor vascularization; neovascularization (pathology); cell motility; protein p130; retinoblastoma-like protein p130; vasculotropin receptor 1; laminin; cancer transplantation; cdkn1b protein, mouse; antigens, cd11b; hypophysis; pituitary gland; proteoglycans; proteoglycan; protein p130rb2
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