Wilms' tumor growth is suppressed by antiangiogenic pigment epithelium-derived factor in a xenograft model. J Pediatr Surg 2003 Mar;38(3):336-42; discussion 336-42
Date
03/13/2003Pubmed ID
12632345DOI
10.1053/jpsu.2003.50104Scopus ID
2-s2.0-0037371954 (requires institutional sign-in at Scopus site) 61 CitationsAbstract
BACKGROUND/PURPOSE: 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.
Author List
Abramson LP, Stellmach V, Doll JA, Cornwell M, Arensman RM, Crawford SEAuthor
Jennifer A. Doll PhD Assistant Professor in the Biomedical Sciences department at University of Wisconsin - MilwaukeeMESH terms used to index this publication - Major topics in bold
Angiogenesis InhibitorsAnimals
Eye Proteins
Humans
Kidney
Kidney Neoplasms
Mice
Mice, Knockout
Mice, Nude
Mitotic Index
Neoplasm Transplantation
Neovascularization, Pathologic
Nerve Growth Factors
Proteins
Recombinant Proteins
Serpins
Tumor Cells, Cultured
Wilms Tumor
Xenograft Model Antitumor Assays
