Importance of vascular endothelial growth factor A in the progression of experimental neuroblastoma

被引：23

作者：

Bäckman U. ^{[1
]}

Svensson Å. ^{[1
]}

Christofferson R. ^{[2
]}

机构：

[1] Department of Medical Cell Biology, Children's Hospital, Uppsala University

[2] Department of Surgical Sciences, Children's Hospital, Uppsala University

来源：

Angiogenesis | 2002年 / 5卷 / 4期

关键词：

Angiogenesis; Neuroblastoma; SH-SY5Y; SU5416; VEGF-A;

D O I：

10.1023/A:1024564817563

中图分类号：

学科分类号：

摘要：

Vascular endothelial growth factor A (VEGF-A) and its receptor tyrosine kinases located on endothelial cells seem to play an important role in the multistep pathway of angiogenesis. SU5416 is a small molecule which inhibits angiogenesis by acting as an inhibitor of VEGF receptor-2 tyrosine kinase. We have developed a reproducible murine model for neuroblastoma, a childhood cancer, based on s.c. xenotransplantation of SH-SY5Y neuroblastoma cells. We found that SH-SY5Y cells expressed VEGF-A on both the mRNA and protein levels, that plasma concentrations of VEGF-A were significantly elevated in animals with neuroblastoma with a volume > 1.4 ml, and that there was a correlation between VEGF-A levels in plasma and tumor size in untreated tumor-bearing animals. Treatment with SU5416 reduced the growth of neuroblastoma tumors by 65% without apparent toxicity. SU5416 treatment also suppressed tumor angiogenesis, despite an increase in plasma VEGF-A levels per ml tumor volume during therapy. Our experimental data suggest that the angiogenesis inhibitor SU5416 may be beneficial in the treatment of solid tumors of childhood such as neuroblastoma.

引用

页码：267 / 274

页数：7

共 34 条

[1]

Bertholdt F., Hero B., Neuroblastoma: Current drug therapy recommendations as part of the total treatment approach, Drugs, 59, pp. 1261-1277, (2000)

[2]

Folkman J., Tumor angiogenesis: Therapeutic implications, N Engl J Med, 285, pp. 1182-1186, (1971)

[3]

Ferrara N., Vascular endothelial growth factor and the regulation of angiogenesis, Recent Prog Horm Res, 55, pp. 15-35, (2000)

[4]

Dirix L.Y., Vermeulen P.B., Pawinski A., Et al., Elevated levels of the angiogenic cytokines basic fibroblast growth factor and vascular endothelial growth factor in sera of cancer patients, Br J Cancer, 76, pp. 238-243, (1997)

[5]

Cherrington J.M., Strawn L.M., Shawver L.K., New paradigms for the treatment of cancer: The role of anti-angiogenesis agents, Adv Cancer Res, 79, pp. 1-38, (2000)

[6]

Barleon B., Hauser S., Schoellmann C., Et al., Differential expression of the two VEGF receptors flt and KDR in placenta and vascular endothelial cells, J Cell Biochem, 54, pp. 56-66, (1994)

[7]

Presta L.G., Chen H., O'Connor S.J., Et al., Humanization of an antivascular endothelial growth factor monoclonal antibody for the therapy of solid tumors and other disorders, Cancer Res, 57, pp. 4593-4599, (1997)

[8]

Mordenti A., Thomsen K., Licko V., Et al., Efficacy and concentration-response of murine anti-VEGF monoclonal antibody in tumor-bearing mice and extrapolation to humans, Toxicol Pathol, 27, pp. 14-21, (1999)

[9]

De Vries C., Escobedo J.A., Ueno H., Et al., The fms-like tyrosine kinase, a receptor for vascular endothelial growth factor, Science, 255, pp. 989-991, (1992)

[10]

Terman B.I., Dougher-Vermazen M., Carrion M.E., Et al., Identification of the KDR tyrosine kinase as receptor for vascular endothelial growth factor, Biochem Biophys Res Commun, 187, pp. 1579-1586, (1992)

← 1 2 3 4 →