Pathways for aberrant angiogenesis in pancreatic cancer

被引:129
作者
M Korc
机构
[1] Div. of Endocrinol. Diabetes/Metab., Department of Medicine, University of California, Irvine
关键词
Vascular Endothelial Growth Factor; Pancreatic Cancer; Hepatocyte Growth Factor; Pancreatic Cancer Cell; Pancreatic Cancer Cell Line;
D O I
10.1186/1476-4598-2-8
中图分类号
学科分类号
摘要
Pancreatic ductal adenocarcinoma (PDAC) is a devastating disease. Although the specific mechanisms that dictate its biological aggressiveness are not clearly established, it is characterized by a variety of molecular alterations as well as by the overexpression of mitogenic and angiogenic growth factors and their receptors. PDACs also express high levels of vascular endothelial growth factor (VEGF). Recent studies indicate that suppression of VEGF expression attenuates pancreatic cancer cell tumorigenicity in a nude mouse model, and that VEGF can exert direct mitogenic effects on some pancreatic cancer cells. These findings suggest that cancer cell derived VEGF promotes pancreatic cancer growth in vivo via a paracrine angiogenic pathway and an autocrine mitogenic pathway, and provide novel opportunities for therapeutic intervention in this deadly disease. © 2003 Korc; licensee BioMed Central Ltd.
引用
收藏
页数:8
相关论文
共 145 条
[131]  
Liu D., EGFR is a transducer of the urokinase receptor initiated signal that is required for in vivo growth of a human carcinoma, Cancer Cell, 1, 5, pp. 445-457, (2002)
[132]  
Bancroft C.C., Effects of pharmacologic antagonists of epidermal growth factor receptor, PI3K and MEK signal kinases on NF-kappaB and AP-1 activation and IL-8 and VEGF expression in human head and neck squamous cell carcinoma lines, Int. J. Cancer, 99, 4, pp. 538-548, (2002)
[133]  
Hirata A., ZD1839 (Iressa) induces antiangiogenic effects through inhibition of epidermal growth factor receptor tyrosine kinase, Cancer Res., 62, 9, pp. 2554-2560, (2002)
[134]  
Tsuzuki Y., Pancreas microenvironment promotes VEGF expression and tumor growth: Novel window models for pancreatic tumor angiogenesis and microcirculation, Lab. Invest., 81, 10, pp. 1439-1451, (2001)
[135]  
Yamanaka Y., Synthesis and expression of transforming growth factor beta-1, beta-2, and beta-3 in the endocrine and exocrine pancreas, Diabetes, 42, 5, pp. 746-756, (1993)
[136]  
Reinmuth N., Impact of insulin-like growth factor receptor-I function on angiogenesis, growth, and metastasis of colon cancer, Lab. Invest., 82, 10, pp. 1377-1389, (2002)
[137]  
Reinmuth N., Blockade of insulin-like growth factor I receptor function inhibits growth and angiogenesis of colon cancer, Clin. Cancer Res., 8, 10, pp. 3259-3269, (2002)
[138]  
Teraoka H., Enhanced VEGF production and decreased immunogenicity induced by TGF-beta 1 promote liver metastasis of pancreatic cancer, Br. J. Cancer, 85, 4, pp. 612-617, (2001)
[139]  
Ebert M.P., Reduced PTEN expression in the pancreas overexpressing transforming growth factor-beta 1, Br. J. Cancer, 86, 2, pp. 257-262, (2002)
[140]  
Bergers G., Matrix metalloproteinase-9 triggers the angiogenic switch during carcinogenesis, Nat. Cell Biol., 2, 10, pp. 737-744, (2000)