Wilms' tumor growth is suppressed by antiangiogenic pigment epithelium-derived factor in a xenograft model.
OBJECTIVE
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/C57Bl6 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.
Abramson
Lisa P
LP
Division of Pediatric Surgery, Children's Memorial Hospital, and the Department of Pathology, Northwestern University Medical School, Chicago, Illinois 60611, USA.
Stellmach
Veronica
V
Doll
Jennifer A
JA
Cornwell
Mona
M
Arensman
Robert M
RM
Crawford
Susan E
SE
D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D000818:Animals; D005136:Eye Proteins; D006801:Humans; D007668:Kidney / Q000098:blood supply / Q000378:metabolism; D007680:Kidney Neoplasms / Q000098:blood supply / Q000188:drug therapy* / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D008819:Mice, Nude; D008940:Mitotic Index; D009368:Neoplasm Transplantation; D009389:Neovascularization, Pathologic / Q000188:drug therapy*; D009414:Nerve Growth Factors; D011506:Proteins / Q000235:genetics / Q000378:metabolism / Q000627:therapeutic use*; D011994:Recombinant Proteins / Q000627:therapeutic use; D015843:Serpins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism / Q000627:therapeutic use*; D014407:Tumor Cells, Cultured / Q000637:transplantation; D009396:Wilms Tumor / Q000098:blood supply / Q000188:drug therapy* / Q000473:pathology; D023041:Xenograft Model Antitumor Assays; D000099174:Pigment Epithelium-Derived Factor
D020533:Angiogenesis Inhibitors; D005136:Eye Proteins; D009414:Nerve Growth Factors; D011506:Proteins; D011994:Recombinant Proteins; D015843:Serpins; D000099174:Pigment Epithelium-Derived Factor