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The class VI intermediate filament protein, nestin is reported to be a progenitorcell marker in various tissues. In the present study, we analyzed the expressionand roles of nestin in angiogenesis of pancreatic ductal adenocarcinomas, anddetermined whether nestin is a potential target for inhibiting tumor angiogenesisusing a gene silencing strategy. Nestin expression was detected only in smallvessels, whereas CD34, CD31 and factor VIII were also expressed in large-sizedblood vessels in PDAC. The number of nestin-positive vessels was approximately20% the number of CD34-positive vessels, and the average dimension of nestin-positivevessels was approximately 75% that of CD34-positive vessels. The PCNA labelingindices of nestin-positive vessels were higher than those of CD34-positive vesselsand nestin-negative vessels. Reducing nestin expression by use of siRNA targetingnestin transcripts inhibited growth of the vascular endothelial cell lines, butthere was no difference in cell motility. In xenograft models, administrationof siRNA targeting mouse-nestin suppressed subcutaneous human pancreatic cancercell growth in nude mice. In conclusion, nestin was expressed in small proliferatingblood vessels in pancreatic cancer tissues and may be a useful marker of angiogenesisin pancreatic ductal adenocarcinoma tissues. Furthermore, nestin is a potentialnovel therapeutic target in pancreatic cancers to inhibit tumor angiogenesis.

Nestin as a novel therapeutic target for pancreatic cancer via tumor angiogenesis