Aberrant Expression of Neuropilin-1 and -2 in Human Pancreatic Cancer Cells

Abstract

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.

Drug-induced expression of the cellular adhesion molecule L1CAM confers anti-apoptotic protection and chemoresistance in pancreatic ductal adenocarcinoma cells

“…NO synthesis can be induced by interaction of L1CAM and neuropilin-1 on one cell (cis) or by interaction of both molecules on different cells (trans). Moreover, it has been shown that PDAC cells highly express neuropilin-1 (Fukahi et al, 2004) and that overexpression of neuropilin-1 is able to induce chemoresistance in PDAC cells (Wey et al, 2005). As both PT45-P1res and PT45-P1 cells exhibit neuropilin-1 expression (unpublished observation), it seems likely that cis and trans interactions of neuropilin-1 with L1CAM increase iNOS expression and NO synthesis, thereby leading to chemoresistance in PT45-P1res cells.…”

Autocrine semaphorin 3A signaling promotes glioblastoma dispersal

“…Accumulating evidence suggests that neuropilin-1 is overexpressed in several cancers and its high expression is correlated with poor prognosis (Ding et al, 2000;Kawakami et al, 2002;Roche et al, 2002;Vanveldhuizen et al, 2003;Broholm and Laursen, 2004;Fukahi et al, 2004;Li et al, 2004;Osada et al, 2004;Parikh et Figure 8 Semaphorin3A (Sema3A) expression in human glioblastoma multiformes (GBMs). (a) Immunohistochemical analysis of Sema3A in human GBM tissue.…”

Pancreatic cancer microenvironment

“…Likewise, genetic targeting of VEGF-RII has been shown to inhibit local growth and metastatic spread of pancreatic cancer cells. 69 Other angiogenic proteins that have been identified as negative prognostic factors in PDAC include cyclooxygenase-2, 70 neuropilin-1 (NRP-1), 71 and others. Interestingly, angiogenic receptors may not only be expressed on endothelium but are also present and functional in pancreatic cells.…”