title: p130Rb2 and p27kip1 cooperate to control mobilization of angiogenic progenitors from the bone marrow.
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.
authors.affiliation: Department of Molecular Biology, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10021, USA.
authors.forename: Anxo
authors.initials: A
authors.lastname: Vidal
authors.forename: Stergios
authors.initials: S
authors.lastname: Zacharoulis
authors.forename: Wenjun
authors.initials: W
authors.lastname: Guo
authors.forename: David
authors.initials: D
authors.lastname: Shaffer
authors.forename: Filippo
authors.initials: F
authors.lastname: Giancotti
authors.forename: Anna H
authors.initials: AH
authors.lastname: Bramley
authors.forename: Carmen
authors.initials: C
authors.lastname: de la Hoz
authors.forename: Kristian K
authors.initials: KK
authors.lastname: Jensen
authors.forename: Daniel
authors.initials: D
authors.lastname: Kato
authors.forename: Daniel D
authors.initials: DD
authors.lastname: MacDonald
authors.forename: Joseph
authors.initials: J
authors.lastname: Knowles
authors.forename: Nancy
authors.initials: N
authors.lastname: Yeh
authors.forename: Lawrence A
authors.initials: LA
authors.lastname: Frohman
authors.forename: Shahin
authors.initials: S
authors.lastname: Rafii
authors.forename: David
authors.initials: D
authors.lastname: Lyden
authors.forename: Andrew
authors.initials: A
authors.lastname: Koff
mesh_terms: D000818:Animals; D001853:Bone Marrow / Q000378:metabolism / Q000473:pathology; D001854:Bone Marrow Cells / Q000166:cytology / Q000473:pathology*; D039481:CD11b Antigen / Q000096:biosynthesis; D018797:Cell Cycle Proteins / Q000378:metabolism / Q000502:physiology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002478:Cells, Cultured; D003094:Collagen / Q000494:pharmacology; D050760:Cyclin-Dependent Kinase Inhibitor p27; D004338:Drug Combinations; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism; D005434:Flow Cytometry; D007797:Laminin / Q000494:pharmacology; D051379:Mice; D008822:Mice, Transgenic; D009368:Neoplasm Transplantation; D009389:Neovascularization, Pathologic; D010902:Pituitary Gland / Q000378:metabolism; D011506:Proteins / Q000378:metabolism / Q000502:physiology*; D011509:Proteoglycans / Q000494:pharmacology; D050717:Retinoblastoma-Like Protein p130; D013997:Time Factors; D025521:Tumor Suppressor Proteins / Q000378:metabolism / Q000502:physiology*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000096:biosynthesis / Q000378:metabolism; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism
chemical_list: D039481:CD11b Antigen; C493961:Cdkn1b protein, mouse; D018797:Cell Cycle Proteins; D004338:Drug Combinations; D007797:Laminin; D011506:Proteins; D011509:Proteoglycans; D050717:Retinoblastoma-Like Protein p130; D025521:Tumor Suppressor Proteins; D042461:Vascular Endothelial Growth Factor A; C059485:matrigel; D050760:Cyclin-Dependent Kinase Inhibitor p27; D003094:Collagen; D040281:Vascular Endothelial Growth Factor Receptor-1; D040301:Vascular Endothelial Growth Factor Receptor-2