Wilms' tumor growth is suppressed by antiangiogenic pigment epithelium-derived factor in a xenograft model

Lisa P. Abramson, Veronica Stellmach, Jennifer A. Doll, Mona Cornwell, Robert M. Arensman, Susan E. Crawford, Henri Ford

Research output: Contribution to journalArticle

55 Scopus citations

Abstract

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/C57BI6 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.

Original languageEnglish (US)
Pages (from-to)336-342
Number of pages7
JournalJournal of Pediatric Surgery
Volume38
Issue number3
DOIs
StatePublished - Mar 1 2003
Externally publishedYes

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Keywords

  • Anaplasia
  • Angiogenesis inhibitors
  • Pigment epithelium-derived factor
  • Wilms' tumor
  • Xenograft

ASJC Scopus subject areas

  • Surgery
  • Pediatrics, Perinatology, and Child Health

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