Pancreatic carcinoma cells express neuropilins and vascular endothelial growth factor, but not vascular endothelial growth factor receptors
Year: 2004
Type: article
Abstract: BACKGROUND: Neuropilins (NRPs) are characterized as coreceptors of vascular endothelial growth factor (VEGF). In the current study, the authors assessed the expression of NRPs, VEGF, and vascular endothelial growth factor receptors (VEGFRs), as well as VEGF-induced cell proliferation, in pancreatic carcinoma cell lines and tissue specimens. METHODS: Human pancreatic carcinoma cell lines (Panc-1 and MIA PaCa-2), normal human pancreatic ductal epithelial cells (HPDE), and human umbilical vein endothelial cells (HUVECs) were cultured. Human pancreatic adenocarcinoma tissue specimens were also studied. Expression levels of NRPs, VEGFRs, and VEGF were determined by real-time polymerase chain reaction analysis and immunostaining. Cell proliferation was examined using a [3H]thymidine incorporation assay. RESULTS: Both NRP-1 and NRP-2 were expressed in Panc-1 cells, HPDE cells, and HUVECs but were expressed minimally in MIA PaCa-2 cells. Panc-1 expressed 30 times more NRP-1 mRNA than NRP-2 mRNA. NRP-1 levels in Panc-1 cells were 5.3 times higher than in HPDE cells but were similar to NRP-1 levels in HUVECs. NRP-2 levels in Panc-1 cells were similar to NRP-2 levels in HPDE cells but lower than NRP-2 levels in HUVECs. Expression of all three VEGFRs was observed only in HUVECs. However, VEGF mRNA was detected in all cell types except for HUVECs. NRP-1 immunoreactivity levels were much higher than NRP-2 immunoreactivity levels in Panc-1 and human pancreatic adenocarcinoma tissue specimens, whereas VEGFRs were not detected in either of these two settings. In response to VEGF165, [3H]thymidine incorporation in Panc-1 cells increased significantly (by 61%; P < 0.01). A monoclonal antibody against human NRP-1 significantly blocked VEGF-induced cell proliferation in Panc-1 cells. CONCLUSIONS: The pancreatic carcinoma cell line Panc-1 and adenocarcinoma tissue specimens expressed high levels of NRP-1 and VEGF, but not VEGFRs, and exogenous VEGF significantly increased NRP-1-mediated, but not VEGFR-mediated, Panc-1 cell proliferation. These data suggested that NRP-1 may be involved in the pathogenesis of pancreatic carcinoma.
Source: Cancer
DOI: 10.1002/cncr.20634
Institutions: Houston Methodist, Baylor College of Medicine
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: bronze
Awards: G1344448503, G190228119, G1915656849, G2000094705, G2019773101, HIV PROTEASE INHIBITORS EFFECT--NENDOTHELIAL DYSFUNCTION, Role of Somatostatin Receptors in Pancreatic Cancer, Effects of HIV Protease Inhibitors of Endothelial Barrie, G286589514, G323822433, Intraislet Communication in Surgically-Altered Pancreas, G3660673002, Molecular Surgeon Symposium on Pancreatic Cancer, ANGIOTENSIN II AND REGULATION OF MCP-1 GENE EXPRESSION, HIV/SIV ENVELOPE GLYCOPROTEIN EFFECTS ON ENDOTHELIA, Influenza HA in SHIV VLPS for mucosal vaccination, PDX-1 is a Therapeutic Target for Pancreatic Cancer, G5386019731, G606007634, ENHANCEMENT OF HIV IMMUNOGENICITY BY INFLUENZA VIRUS, G9000140323, G9000149727, G9000306400
OpenAlex ID: W2034391789