Concomitant over-expression of vascular endothelial growth factor and its receptors in pancreatic cancer

✍ Scribed by Jun Itakura; Toshiyuki Ishiwata; Ben Shen; Marko Kornmann; Murray Korc

• Publisher: John Wiley and Sons
• Year: 2000
• Tongue: French
• Weight: 443 KB
• Volume: 85
• Category: Article
• ISSN: 0020-7136
• DOI: 10.1002/(sici)1097-0215(20000101)85:1<27::aid-ijc5>3.0.co;2-8

✦ Synopsis

Vascular endothelial growth factor (VEGF) is a potent angiogenic polypeptide that activates 2 distinct high-affinity tyrosine kinase receptors, flk-1/KDR and flt-1. In the present study, we characterized the expression of VEGF and its receptors flk-1/KDR and flt-1 in the normal human pancreas and in human pancreatic cancer tissues and cell lines. VEGF, flk-1/KDR and flt-1 mRNA levels were elevated in cancer tissues compared with normal pancreas. By immuno-histochemistry, VEGF, flk-1/KDR and flt-1 immunoreactivity colocalized in many of the cancer cells within the tumor mass. Three (AsPC-1, Capan-1 and MIAPaCa-2) of 6 pancreatic cancer cell lines expressed flk-1/KDR mRNA and protein, and 4 cell lines (AsPC-1, Capan-1, T3M4 and PANC-1) expressed flt-1 mRNA transcripts. Binding studies with 125 I-labeled VEGF165 indicated that only Capan-1 cells exhibited high levels of specific binding. Furthermore, VEGF enhanced the growth of Capan-1 cells but was without effect in the other cell lines. VEGF also enhanced mitogen-activated protein kinase (MAPK) phosphorylation and c-fos induction in Capan-1 cells, whereas the MAPK kinase inhibitor PD98059 abolished the growth-stimulatory effect of VEGF. These data indicate that human pancreatic cancers have the capacity to over-express VEGF and its receptors and suggest that in some instances VEGF may directly promote pancreatic cancer growth via the MAPK pathway. Int.