Utilization of bone marrow-derived endothelial cell precursors in spontaneous prostate tumors varies with tumor grade.
Id1 and Id3 genes are required for vascularization, growth, and metastasis of xenograft tumors. In Id-deficient mice, tumor transplantation and proangiogenic factors fail to mobilize and recruit circulating endothelial precursor cells (CEPs) and hematopoietic cells, leading to defective tumor angiogenesis in various models. To investigate the requirement of Id genes and bone marrow incorporation in spontaneous prostate tumors, we crossbred Id mutant mice with the transgenic adenocarcinoma of the mouse prostate (TRAMP) mice. Id1-/- Id3+/- TRAMP mice display delayed tumor growth at 24 weeks compared with wild-type TRAMP mice. Id1 and Id3 were strongly expressed in the endothelial cells of poorly differentiated prostate adenocarcinoma but not in the vasculature of well-differentiated tumors, a finding that is corroborated in human prostate tumor samples. In Id-deficient TRAMP mice, the poorly differentiated tumors show extensive hemorrhage, whereas well-differentiated tumors exhibit none. Transplantation with Id wild-type bone marrow significantly reduced the hemorrhage in poorly differentiated prostate adenocarcinomas with bone marrow-derived endothelial cells contributing to 14% of the tumor blood vessels. However, in well-differentiated prostate adenocarcinomas, there was little evidence of bone marrow-derived endothelial cell incorporation. These differences in the expression of Id genes, the effects of Id loss, and the recruitment of bone marrow-derived endothelial precursor cells in tumor vasculature between well-differentiated and poorly differentiated prostate adenocarcinoma suggest that tumor angiogenesis varies depending on the tumor grade.
Li
Haiqing
H
Program of Cell Biology and Genetics, Weill Graduate School of Medical Sciences, Cornell University Medical College, New York, New York 10021, USA.
Gerald
William L
WL
Benezra
Robert
R
D000230:Adenocarcinoma / Q000098:blood supply* / Q000235:genetics / Q000473:pathology*; D000818:Animals; D001854:Bone Marrow Cells / Q000473:pathology*; D016026:Bone Marrow Transplantation; D002454:Cell Differentiation / Q000502:physiology; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000172:deficiency / Q000235:genetics; D004730:Endothelium, Vascular / Q000473:pathology*; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D051798:Inhibitor of Differentiation Protein 1; D051797:Inhibitor of Differentiation Protein 2; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009389:Neovascularization, Pathologic / Q000235:genetics / Q000473:pathology; D011471:Prostatic Neoplasms / Q000098:blood supply* / Q000235:genetics / Q000473:pathology*; D018124:Receptors, Tumor Necrosis Factor / Q000235:genetics; D053219:Receptors, Tumor Necrosis Factor, Member 25; D012097:Repressor Proteins / Q000096:biosynthesis / Q000235:genetics; D014157:Transcription Factors / Q000096:biosynthesis / Q000172:deficiency / Q000235:genetics
D004268:DNA-Binding Proteins; C497455:Idb1 protein, mouse; C497452:Idb2 protein, mouse; D051798:Inhibitor of Differentiation Protein 1; D051797:Inhibitor of Differentiation Protein 2; D018124:Receptors, Tumor Necrosis Factor; D053219:Receptors, Tumor Necrosis Factor, Member 25; D012097:Repressor Proteins; C506033:TNFRSF25 protein, human; C506034:Tnfrsf25 protein, mouse; D014157:Transcription Factors