Wilms' tumor growth is suppressed by antiangiogenic pigment epithelium-derived factor in a xenograft model
Wilms' tumor growth is suppressed by antiangiogenic pigment epithelium-derived factor in a xenograft model
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DOI：
10.1053/jpsu.2003.50104
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发表时间：
2003-03-01
影响因子：
2.4
通讯作者：
Crawford, SE
中科院分区：
文献类型：
--
作者：
Abramson, LP;Stellmach, V;Crawford, SE
背景/目的：色素上皮衍生因子（PEDF）是一种有效的内源性血管生成抑制剂，在肾脏中高表达。作者推测，PEDF的全身给药将减少肾母细胞瘤在异种移植模型中的生长，并且增加肾血管分布将导致小鼠对PEDF.Methods无效：使用人间变性肾母细胞瘤细胞在无胸腺小鼠中诱导肿瘤。在接种后2至3周开始施用纯化的PEDF蛋白或载体7天。肿瘤用抗PEDF和抗因子VIII抗体染色。计算每个高倍视野（hpf）的核分裂数和微血管密度（MVD）。在SV 129/C57 B16背景下产生PEDF-无效小鼠。结果：2周组的平均肿瘤重量比对照组低60%（P <0.05）。治疗组的MVD和核分裂计数均显著低于对照组（P <0.05）。PEDF在正常肾脏中染色强烈，但在肾母细胞瘤中染色极轻微或不存在。结论：PEDF在正常小鼠肾组织中表达较强，其血管抑制活性的丧失可能是肾母细胞瘤病理性血管生成的重要原因。系统性PEDF通过靶向肿瘤细胞及其相关血管抑制WT生长。版权所有2003，爱思唯尔科学（美国）。All rights reserved.
Background/Purpose: Pigment epithelium-derived factor (PEDF), a potent endogenous inhibitor of angiogenesis, is highly expressed in the kidney. The authors postulated that systemic administration of PEDF would decrease Wilms' tumor growth in a xenograft model, and increased renal vascularity would result in a mouse null for PEDF.Methods: Tumors were induced in athymic mice using human anaplastic Wilms' tumor cells. Purified PEDF protein or vehicle was administered for 7 days beginning 2 to 3 weeks after inoculation. Tumors were stained with anti-PEDF and anti-Factor VIII antibodies. Mitoses and microvascular density (MVD) were counted per high-power field (hpf). PEDF-null mice were generated on a SV129/C57B16 background. Wild-type and null kidneys were assessed for MVD.Results: Mean tumor weight in the 2-week group was 60% less than controls (P < .05). The MVD and mitotic count in treated tumors were significantly less than controls (P < .05). PEDF stained strongly in normal kidneys but was minimal to absent in Wilms' tumor. PEDF-null kidneys had increased MVD compared with wild-type (P < .05).Conclusions: PEDF is expressed strongly in normal murine kidney, and loss of its angioinhibitory activity may contribute to pathologic angiogenesis in Wilms' tumor. Systemic PEDF suppresses WT growth by targeting both the tumor cells and its associated vasculature. Copyright 2003, Elsevier Science (USA). All rights reserved.