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  • Title: Pigment epithelium-derived factor targets endothelial and epithelial cells in Wilms' tumor.
    Author: Abramson LP, Browne M, Stellmach V, Doll J, Cornwell M, Reynolds M, Arensman RM, Crawford SE.
    Journal: J Pediatr Surg; 2006 Aug; 41(8):1351-6. PubMed ID: 16863836.
    Abstract:
    PURPOSE: Loss of pigment epithelium-derived factor (PEDF), a potent inhibitor of angiogenesis, has been linked to progression of angiogenesis-dependent diseases. We postulated that decreased levels of endogenous PEDF in the kidney creates a tumor permissive environment for Wilms' tumor. METHODS: Fresh and frozen Wilms' tumor (n = 28), adjacent (n = 3), and normal kidney (n = 8) were immunostained and graded. The Wilms' tumor cells (SK-NEP-1), renal epithelial cells (NRK-52), and fresh tumor samples were grown in culture. Condition media were collected and analyzed by an in vitro angiogenesis assay and Western blot. The SK-NEP-1 cells were treated with PEDF and cell viability assessed. RESULTS: Wilms' tumors expressed less PEDF than normal and adjacent kidney. Pigment epithelium-derived factor protein secretion was abundant in NRK-52 cells but significantly decreased in Wilms' tumor. Pigment epithelium-derived factor acted as blockade to angiogenesis and it had a dose-dependent cytotoxic effect on Wilms' tumor epithelial cells. CONCLUSION: Renal tubular epithelial cells are a rich source of PEDF in the normal kidney. Reduced levels of PEDF in Wilms' tumor remove a critical endogenous renal barrier to angiogenesis and tumor cell survival. Therapeutic replacement of PEDF may prove to be an effective strategy to combat Wilms' tumor progression.
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