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

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.