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Updated: Aug 27, 2026
A Melanoma Patient-Derived Xenograft Model
Published on: May 20, 2019
Wilms' tumor growth is suppressed by antiangiogenic pigment epithelium-derived factor in a xenograft model
Lisa P Abramson1, Veronica Stellmach, Jennifer A Doll
1Division of Pediatric Surgery, Children's Memorial Hospital, and the Department of Pathology, Northwestern University Medical School, Chicago, Illinois 60611, USA.
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.
Insights
Pigment epithelium-derived factor (PEDF) inhibits tumor growth and vascularity in Wilms' tumors. Loss of PEDF in kidneys correlates with increased vascularity, suggesting its role in angiogenesis.
Area of Science:
- Oncology
- Nephrology
- Angiogenesis Research
Background:
- Pigment epithelium-derived factor (PEDF) is a natural inhibitor of blood vessel formation (angiogenesis).
- PEDF is highly present in healthy kidney tissue.
- Wilms' tumor, a pediatric kidney cancer, exhibits abnormal angiogenesis.
Purpose of the Study:
- To investigate the effect of systemic Pigment epithelium-derived factor (PEDF) administration on Wilms' tumor growth in a mouse model.
- To examine the role of PEDF in kidney vascularity using genetically modified mice lacking the PEDF gene.
Main Methods:
- Human anaplastic Wilms' tumor cells were used to induce tumors in athymic mice.
- Mice received either purified PEDF protein or a placebo for seven days.
- Tumor microvascular density (MVD) and mitotic activity were quantified.
- PEDF-null mice were generated and their kidney vascularity was compared to wild-type mice.
Main Results:
- Systemic PEDF administration significantly reduced Wilms' tumor weight by 60% compared to controls.
- Treated tumors showed decreased microvascular density (MVD) and mitotic counts.
- PEDF was abundant in normal kidneys but scarce in Wilms' tumors.
- PEDF-null mouse kidneys exhibited significantly higher MVD than wild-type kidneys.
Conclusions:
- Loss of Pigment epithelium-derived factor (PEDF) may promote pathological angiogenesis in Wilms' tumor.
- Systemic PEDF administration effectively suppresses Wilms' tumor growth by targeting both tumor cells and their associated blood vessels.
- PEDF plays a crucial role in regulating renal vascularity.
