Thalidomide is anti-angiogenic in a xenograft model of neuroblastoma.
Thalidomide has previously been shown to have anti-angiogenic properties. More recently, clinical efficacy of this agent has been demonstrated in multiple myeloma and prostate cancer. Neuroblastoma is the most frequent solid tumor of the abdomen of childhood, yet children with this disease frequently have metastases at presentation. Such patients have a very poor prognosis with current therapies. Thus, new approaches are needed. We have previously shown that VEGF antagonists can inhibit neoangiogenesis and tumor growth in experimental neuroblastoma. In this study, we investigated the anti-angiogenic and anti-tumor properties of thalidomide in a xenograft model of human neuroblastoma. Tumors were induced in athymic mice using the human neuroblastoma cell line NGP. Intraperitoneal thalidomide (100 mg/kg/dose) or vehicle was administered beginning one week after implantation, and animals euthanized at six weeks. Thalidomide treatment did not significantly alter tumor growth as compared with controls. However, thalidomide suppressed angiogenesis, as demonstrated both by fluorescein angiography and immunohistochemical staining, and induced apoptosis of endothelial cells in neuroblastoma xenografts. Quantification of microvessel density demonstrated a significant reduction of vasculature in treated tumors (p<0.004). Thalidomide induced co-option of host vasculature, an effect noted previously after VEGF blockade. This study demonstrates that thalidomide has anti-angiogenic properties in experimental neuroblastoma.
Kaicker
Shipra
S
Division of Pediatric Oncology, College of Physicians and Surgeons of Columbia University, New York, NY 10032, USA.
McCrudden
Kimberly W
KW
Beck
Leal
L
New
Tamara
T
Huang
Jianzhong
J
Frischer
Jason S
JS
Serur
Anna
A
Kadenhe-Chiweshe
Angela
A
Yokoi
Akiko
A
Kandel
Jessica J
JJ
Yamashiro
Darrell J
DJ
D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D000818:Animals; D045744:Cell Line, Tumor; D004730:Endothelium, Vascular / Q000166:cytology; D006801:Humans; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D051379:Mice; D008819:Mice, Nude; D009130:Muscle, Smooth / Q000473:pathology; D009368:Neoplasm Transplantation; D009389:Neovascularization, Pathologic; D009447:Neuroblastoma / Q000188:drug therapy*; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000096:biosynthesis; D013792:Thalidomide / Q000494:pharmacology*
D020533:Angiogenesis Inhibitors; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D013792:Thalidomide