p130Rb2 and p27kip1 cooperate to control mobilization of angiogenic progenitors from the bone marrow.
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.
Vidal
Anxo
A
Department of Molecular Biology, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10021, USA.
Zacharoulis
Stergios
S
Guo
Wenjun
W
Shaffer
David
D
Giancotti
Filippo
F
Bramley
Anna H
AH
de la Hoz
Carmen
C
Jensen
Kristian K
KK
Kato
Daniel
D
MacDonald
Daniel D
DD
Knowles
Joseph
J
Yeh
Nancy
N
Frohman
Lawrence A
LA
Rafii
Shahin
S
Lyden
David
D
Koff
Andrew
A
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
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