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.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Bone Marrow / metabolism
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Bone Marrow / pathology
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Bone Marrow Cells / cytology
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Bone Marrow Cells / pathology*
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CD11b Antigen / biosynthesis
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Cell Cycle Proteins / metabolism
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Cell Cycle Proteins / physiology*
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Cell Line, Tumor
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Cell Proliferation
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Cells, Cultured
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Collagen / pharmacology
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Cyclin-Dependent Kinase Inhibitor p27
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Drug Combinations
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Endothelium, Vascular / cytology
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Endothelium, Vascular / metabolism
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Flow Cytometry
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Laminin / pharmacology
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Mice
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Mice, Transgenic
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Neoplasm Transplantation
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Neovascularization, Pathologic*
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Pituitary Gland / metabolism
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Proteins / metabolism
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Proteins / physiology*
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Proteoglycans / pharmacology
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Retinoblastoma-Like Protein p130
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Time Factors
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Tumor Suppressor Proteins / metabolism
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Tumor Suppressor Proteins / physiology*
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Vascular Endothelial Growth Factor A / metabolism
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Vascular Endothelial Growth Factor Receptor-1 / biosynthesis
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Vascular Endothelial Growth Factor Receptor-1 / metabolism
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Vascular Endothelial Growth Factor Receptor-2 / metabolism
Substances
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CD11b Antigen
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Cdkn1b protein, mouse
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Cell Cycle Proteins
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Drug Combinations
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Laminin
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Proteins
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Proteoglycans
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Retinoblastoma-Like Protein p130
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Tumor Suppressor Proteins
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Vascular Endothelial Growth Factor A
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matrigel
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Cyclin-Dependent Kinase Inhibitor p27
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Collagen
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Vascular Endothelial Growth Factor Receptor-1
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Vascular Endothelial Growth Factor Receptor-2