Pigment epithelium-derived factor targets endothelial and epithelial cells in Wilms' tumor

Lisa P. Abramson, Marybeth Browne, Veronica Stellmach, Jennifer Doll, Mona Cornwell, Marleta Reynolds, Robert M. Arensman, Susan E. Crawford*

*Corresponding author for this work

Research output: Contribution to journalArticle

15 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1351-1356
Number of pages6
JournalJournal of pediatric surgery
Volume41
Issue number8
DOIs
StatePublished - Aug 1 2006

Keywords

  • Endothelial cells
  • Epithelial cells
  • Pigment epithelium-derived factor
  • Wilms' tumor

ASJC Scopus subject areas

  • Surgery
  • Pediatrics, Perinatology, and Child Health

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    Abramson, L. P., Browne, M., Stellmach, V., Doll, J., Cornwell, M., Reynolds, M., Arensman, R. M., & Crawford, S. E. (2006). Pigment epithelium-derived factor targets endothelial and epithelial cells in Wilms' tumor. Journal of pediatric surgery, 41(8), 1351-1356. https://doi.org/10.1016/j.jpedsurg.2006.04.038