Expression and regulation of the novel vascular endothelial growth factor receptor neuropilin‐1 by epidermal growth factor in human pancreatic carcinoma
Open Access
- 23 June 2003
- Vol. 98 (4) , 720-729
- https://doi.org/10.1002/cncr.11560
Abstract
BACKGROUND: It was recently shown that neuropilin‐1 (NRP‐1), which was described originally as a receptor for the semaphorins/collapsins (ligands involved in neuronal guidance), is a coreceptor for vascular endothelial growth factor (VEGF) and increases the affinity of specific isoforms of VEGF to its receptor, VEGF‐R2.METHODS: The authors investigated the expression and regulation of NRP‐1 in human pancreatic adenocarcinoma specimens and cell lines.RESULTS: Immunohistochemical analysis revealed that NRP‐1 was expressed in 12 of 12 human pancreatic adenocarcinoma specimens but was absent in nonmalignant pancreatic tissue. Northern blot analysis revealed NRP‐1 mRNA expression in 8 of 11 human pancreatic adenocarcinoma cell lines. NRP‐1 mRNA expression was increased by epidermal growth factor (EGF) but not by tumor necrosis factor α in several of the human pancreatic adenocarcinoma cell lines studied. Treating human Panc‐48 adenocarcinoma cells with EGF activated Akt and Erk but not P‐38. Blockade of the phosphatidylinositol‐3 kinase (PI‐3K)/Akt, mitogen‐activated protein kinase (MAPK)/Erk, or P‐38 pathways abrogated EGF‐induced NRP‐1 expression. Finally, EGF receptor blockade in vivo led to a decrease in NRP‐1 expression in an orthotopic model of human pancreatic carcinoma.CONCLUSIONS: NRP‐1 is expressed in most human pancreatic adenocarcinomas and cell lines but not in nonmalignant pancreatic tissue. EGF regulates NRP‐1 expression through the PI‐3K/Akt and MAPK/Erk signaling pathways, and blockade of the EGF receptor is associated with decreased expression of NRP‐1 in vivo. NRP‐1 may act as a coreceptor for VEGF in pancreatic carcinoma, as it does in other tumor systems, thereby enhancing angiogenesis and the effect of VEGF on the growth of pancreatic adenocarcinoma. Cancer 2003;98:720–9. © 2003 American Cancer Society.DOI 10.1002/cncr.11560Keywords
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