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Suppression of primary tumor growth in a mouse model of human neuroblastoma
1Division of Pediatric Surgery, College of Physicians and Surgeons, Columbia University, and Babies & Children's Hospital of New York, New York 10032, USA.
Background/Purpose:
Neuroblastoma is the most common tumor of the abdomen in children. Consistently effective treatments are lacking for aggressive disease. The authors previously reported that therapy with anti-vascular endothelial growth factor (VEGF) antibodies suppresses both growth and metastasis in an experimental model of Wilms' tumor. The authors hypothesized that, in a parallel model of neuroblastoma, anti-VEGF treatment would inhibit (1) growth and (2) metastasis.
Methods:
Primary tumors were established in the kidneys of nude mice. In cohort 1 (n = 42), mice were killed at 3 time-points, and tissues were evaluated histologically. Tumors were assayed for VEGF. In cohort 2 (n = 28), anti-VEGF antibody or vehicle was administered. Tumor weights and the incidence of metastases in the 2 groups were compared. VEGF deposition was evaluated by immunohistochemistry.
Results:
Mice displayed large tumors with liver and lung metastases. VEGF levels in tumors increased over time. Antibody-treated animals displayed significantly smaller tumors, but incidence and size of metastases were unaffected. VEGF was localized to tumor stroma immunohistochemically, with no difference in pattern observed in control and antibody-treated tumors.
Conclusions:
Anti-VEGF antibodies inhibit primary tumor growth in experimental neuroblastoma, but not metastasis. This may contrast with the effect of the same antibody in a parallel model of Wilms' tumor.
Insights
Anti-vascular endothelial growth factor (VEGF) antibodies reduced neuroblastoma tumor growth in mice. However, anti-VEGF therapy did not impact the spread or size of metastases in this experimental model.
Area of Science:
- Oncology
- Experimental Therapeutics
- Cancer Biology
Background:
- Neuroblastoma is a common pediatric abdominal cancer with limited effective treatments for aggressive forms.
- Previous studies showed anti-vascular endothelial growth factor (VEGF) antibodies inhibited growth and metastasis in a Wilms' tumor model.
- The efficacy of anti-VEGF therapy in neuroblastoma models remained to be investigated.
Purpose of the Study:
- To investigate the effect of anti-VEGF antibody treatment on neuroblastoma growth.
- To determine if anti-VEGF therapy inhibits metastasis in a neuroblastoma experimental model.
Main Methods:
- Primary neuroblastoma tumors were established in nude mice.
- Tumor growth, metastasis incidence, and VEGF levels were assessed.
- Immunohistochemistry was used to evaluate VEGF deposition in tumor tissues.
- Mice received either anti-VEGF antibody or a vehicle control.
Main Results:
- Elevated VEGF levels were observed in neuroblastoma tumors over time.
- Anti-VEGF antibody treatment resulted in significantly smaller primary tumors.
- The incidence and size of liver and lung metastases were not affected by anti-VEGF therapy.
- VEGF was localized to the tumor stroma, with no difference between control and treated groups.
Conclusions:
- Anti-VEGF antibodies demonstrate efficacy in inhibiting primary neuroblastoma tumor growth in an experimental setting.
- Anti-VEGF therapy did not significantly affect metastasis in this neuroblastoma model.
- These findings may differ from the effects observed in Wilms' tumor models, suggesting context-dependent efficacy.