All angiogenesis is not the same: Distinct patterns of response to antiangiogenic therapy in experimental neuroblastoma and Wilms tumor.
OBJECTIVE
Neuroblastoma and Wilms tumor exhibit different patterns of metastasis, invasion, and therapeutic response. Vascular endothelial growth factor (VEGF) is an angiogenic factor expressed in both tumors. The authors hypothesized that because the clinical behavior of these tumors differs, the response to anti-VEGF therapy would be distinct, and tumor vascular architectures would reflect this distinction.


METHODS
Xenografts were induced by intrarenal injection of cultured cells in athymic mice. After 1 week, anti-VEGF antibody or vehicle were administered for 5 weeks before sacrifice. Additional animals were maintained for 3 weeks after termination of antibody injections to assess rebound growth of tumors. Fluorescein angiography was performed in selected animals.


RESULTS
Neuroblastoma control and treated tumor weights were not significantly different (1.48 g v 0.77 g, P =.34). By comparison, as previously reported, antibody-treated Wilms tumors were growth inhibited. Angiograms of treated (but not control) neuroblastomas displayed novel rounded structures at vessel branches, which the authors term terminal vascular bodies (TVBs). Wilms tumor vessels displayed no such alteration.


CONCLUSIONS
Neuroblastoma xenografts are less effectively suppressed by anti-VEGF antibody than Wilms tumors. Neuroblastoma vascular architecture displays a novel alteration during antibody administration, which attenuates when antibody is withdrawn. These studies suggest that angiogenesis is differently regulated in experimental neuroblastoma and Wilms tumor.
Kim
E
E
Division of Pediatric Surgery,Department of Pathology, Columbia University, College of Physicians and Surgeons, New York, NY, USA.
Moore
J
J
Huang
J
J
Soffer
S
S
Manley
C A
CA
O'Toole
K
K
Middlesworth
W
W
Stolar
C J
CJ
Kandel
J J
JJ
Yamashiro
D J
DJ
D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D001932:Brain Neoplasms / Q000098:blood supply / Q000628:therapy*; D016228:Endothelial Growth Factors / Q000037:antagonists & inhibitors* / Q000502:physiology; D006801:Humans; D007680:Kidney Neoplasms / Q000098:blood supply / Q000628:therapy*; D051379:Mice; D008819:Mice, Nude; D023421:Models, Animal; D009361:Neoplasm Invasiveness / Q000503:physiopathology; D009389:Neovascularization, Pathologic; D009447:Neuroblastoma / Q000098:blood supply / Q000628:therapy*; D016896:Treatment Outcome; D009396:Wilms Tumor / Q000098:blood supply / Q000628:therapy*
D020533:Angiogenesis Inhibitors; D000911:Antibodies, Monoclonal; D016228:Endothelial Growth Factors