Utilization of bone marrow-derived endothelial cell precursors in spontaneous prostate tumors varies with tumor grade
Utilization of bone marrow-derived endothelial cell precursors in spontaneous prostate tumors varies with tumor grade
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DOI：
10.1158/0008-5472.can-04-1287
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发表时间：
2004-09-01
期刊：
影响因子：
11.2
通讯作者：
Benezra, R
中科院分区：
文献类型：
--
作者：
Li, HQ;Gerald, WL;Benezra, R
Id1 和 Id3 基因是异种移植肿瘤的血管形成、生长和转移所必需的。在Id缺陷小鼠中，肿瘤移植和促血管生成因子无法动员和募集循环内皮前体细胞（CEP）和造血细胞，导致各种模型中肿瘤血管生成缺陷。为了研究自发性前列腺肿瘤对 Id 基因和骨髓掺入的需求，我们将 Id 突变小鼠与转基因小鼠前列腺腺癌 (TRAMP) 小鼠杂交。与野生型 TRAMP 小鼠相比，Id1(-/-) Id3(+/-) TRAMP 小鼠在 24 周时表现出肿瘤生长延迟。 Id1 和 Id3 在低分化前列腺腺癌的内皮细胞中强烈表达，但在高分化肿瘤的脉管系统中不表达，这一发现在人类前列腺肿瘤样本中得到了证实。在Id缺陷的TRAMP小鼠中，分化差的肿瘤表现出广泛的出血，而分化良好的肿瘤则没有表现出出血。 Id野生型骨髓移植显着减少了低分化前列腺腺癌的出血，其中骨髓源性内皮细胞占肿瘤血管的14%。然而，在分化良好的前列腺腺癌中，几乎没有骨髓源性内皮细胞掺入的证据。高分化和低分化前列腺腺癌之间 Id 基因表达、Id 丢失的影响以及肿瘤脉管系统中骨髓来源的内皮前体细胞的募集的这些差异表明肿瘤血管生成根据肿瘤等级而变化。
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.