Aberrant expression of neuropilin-1 and-2 in human pancreatic cancer cells
Aberrant expression of neuropilin-1 and-2 in human pancreatic cancer cells
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DOI：
10.1158/1078-0432.ccr-0930-03
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发表时间：
2004-01-15
影响因子：
11.5
通讯作者：
Korc, M
中科院分区：
文献类型：
--
作者：
Fukahi, K;Fukasawa, M;Korc, M
目的：Neuropilin (Np)-1和-2是血管内皮生长因子（VEGF）的辅助受体。本研究旨在评估它们在胰腺导管腺癌（PDAC）中的作用。实验设计：我们通过实时定量PCR评估Np-1和Np-2表达与胰腺癌细胞系和组织中VEGF配体和受体表达的关系。结果：ASPC-1、CAPAN-1和PANC-1胰腺癌细胞和肿瘤来源的、激光捕获的胰腺癌细胞的Np-1和Np-2 mRNA水平高于VEGF受体-1、-2或-3 mRNA水平。在COS-7细胞中转染Np-1和Np-2 cdna，并用tunicamycin处理，结果显示这两种蛋白都被糖基化了。这两种蛋白在胰腺癌细胞系、PDAC样品和癌细胞附近的腺泡细胞中均有表达。正常胰腺缺乏Np-1免疫反应性，而在内分泌胰岛和一些腺泡细胞中存在Np-2免疫反应性，但在导管细胞中没有。结论：Np-1和Np-2在PDAC癌细胞中的异常定位表明，这些辅助受体除了发挥促血管生成作用外，还可能在这种恶性肿瘤中参与新的自分泌-旁分泌相互作用。
Purpose: Neuropilin (Np)-1 and -2 are coreceptors for vascular endothelial growth factor (VEGF). This study was designed to assess their role in pancreatic ductal adenocarcinoma (PDAC).Experimental Design: We assessed Np-1 and Np-2 expression by real-time quantitative PCR in relation to the expression of VEGF ligands and receptors in pancreatic cancer cell lines and tissues.Results: ASPC-1, CAPAN-1, and PANC-1 pancreatic cancer cells and tumor-derived, laser-captured pancreatic cancer cells exhibited higher Np-1 and Np-2 mRNA levels than VEGF receptor-1, -2, or -3 mRNA levels. Transfection of Np-1 and Np-2 cDNAs in COS-7 cells, and treatment with tunicamycin revealed that both proteins were glycosylated. Both proteins were expressed in pancreatic cancer cell lines, in the PDAC samples, and in acinar cells adjacent to the cancer cells. The normal pancreas was devoid of Np-1 immunoreactivity, whereas Np-2 immunoreactivity was present in the endocrine islets and in some acinar cells, but not in ductal cells.Conclusions: The aberrant localization of Np-1 and Np-2 in the cancer cells in PDAC suggests that in addition to exerting proangiogenic effects, these coreceptors may contribute to novel autocrine-paracrine interactions in this malignancy.