Abramson Lisa P, Stellmach Veronica, Doll Jennifer A, Cornwell Mona, Arensman Robert M, Crawford Susan E
Division of Pediatric Surgery, Children's Memorial Hospital, and the Department of Pathology, Northwestern University Medical School, Chicago, Illinois 60611, USA.
J Pediatr Surg. 2003 Mar;38(3):336-42; discussion 336-42. doi: 10.1053/jpsu.2003.50104.
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.
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/C57Bl6 background. Wild-type and null kidneys were assessed for MVD.
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).
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.
背景/目的：色素上皮衍生因子（PEDF）是一种强大的内源性血管生成抑制剂，在肾脏中高度表达。作者推测，在异种移植模型中全身给予PEDF会减少肾母细胞瘤的生长，而PEDF基因敲除小鼠的肾血管生成增加。
使用人间变性肾母细胞瘤细胞在无胸腺小鼠中诱导肿瘤形成。接种后2至3周开始，给予纯化的PEDF蛋白或赋形剂，持续7天。用抗PEDF和抗因子VIII抗体对肿瘤进行染色。在每个高倍视野（hpf）中计数有丝分裂和微血管密度（MVD）。在SV129/C57Bl6背景上培育PEDF基因敲除小鼠。评估野生型和基因敲除小鼠肾脏的MVD。
2周组的平均肿瘤重量比对照组减少60%（P<.05）。治疗组肿瘤的MVD和有丝分裂计数明显低于对照组（P<.05）。PEDF在正常肾脏中染色强烈，但在肾母细胞瘤中极少或无染色。与野生型相比，PEDF基因敲除小鼠的肾脏MVD增加（P<.05）。
PEDF在正常小鼠肾脏中强烈表达，其血管生成抑制活性的丧失可能导致肾母细胞瘤中的病理性血管生成。全身给予PEDF通过靶向肿瘤细胞及其相关脉管系统来抑制肾母细胞瘤的生长。
