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


CONCLUSIONS
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.
Abramson
Lisa P
LP
Division of Pediatric Surgery, Children's Memorial Hospital, Chicago, IL 60614, USA.
Browne
Marybeth
M
Stellmach
Veronica
V
Doll
Jennifer
J
Cornwell
Mona
M
Reynolds
Marleta
M
Arensman
Robert M
RM
Crawford
Susan E
SE
D000818:Animals; D002465:Cell Movement / Q000502:physiology; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000737:chemistry / Q000187:drug effects*; D004847:Epithelial Cells / Q000737:chemistry / Q000187:drug effects*; D005136:Eye Proteins / Q000032:analysis* / Q000502:physiology*; D006801:Humans; D007668:Kidney / Q000502:physiology; D009414:Nerve Growth Factors / Q000032:analysis* / Q000502:physiology*; D051381:Rats; D015843:Serpins / Q000032:analysis* / Q000502:physiology*; D014407:Tumor Cells, Cultured; D009396:Wilms Tumor / Q000737:chemistry / Q000503:physiopathology*; D000099174:Pigment Epithelium-Derived Factor
D005136:Eye Proteins; D009414:Nerve Growth Factors; D015843:Serpins; D000099174:Pigment Epithelium-Derived Factor