Faculty Collaboration Database

Neuropilin-1 suppresses tumorigenic properties in a human pancreatic adenocarcinoma cell line lacking neuropilin-1 coreceptors. Cancer Res 2005 May 01;65(9):3664-70

Date

05/04/2005

Pubmed ID

15867361

DOI

10.1158/0008-5472.CAN-04-2229

Scopus ID

2-s2.0-18144427143 (requires institutional sign-in at Scopus site)   82 Citations

Abstract

Neuropilin-1 (NRP-1) was first described as a coreceptor implicated in neuronal guidance that bound members of the semaphorin/collapsin family. NRP-1 is also expressed in endothelial cells and is believed to promote angiogenesis by acting as a coreceptor with vascular endothelial growth factor (VEGF) receptor 2. Recent studies suggest that NRP-1 can function through both a VEGF-dependent and VEGF-independent fashion. Expression of NRP-1 has been shown in many human tumors, including pancreatic adenocarcinomas. The exact role of NRP-1 in tumor cells is unknown, particularly in cells that lack the NRP-1 coreceptors VEGF receptor 2 and Plexin-A1. To discern the regulatory role(s) of NRP-1 in pancreatic adenocarcinoma that lack these coreceptors, we overexpressed both full-length NRP-1 and a deletion form of NRP-1 that does not interact with semaphorin or VEGF. Overexpression of either isoform reduced several key tumorigenic properties, including anchorage-independent cell growth and migration in vitro, and resulted in reduced tumor incidence and tumor volume in vivo. Conversely, reduction of NRP-1 expression by small interfering RNA targeting led to enhanced tumor growth. Thus, NRP-1 may play distinct growth regulatory roles in different tumor types, and altering NRP-1 expression or function may be a means of influencing the growth of pancreatic cancers.

Author List

Gray MJ, Wey JS, Belcheva A, McCarty MF, Trevino JG, Evans DB, Ellis LM, Gallick GE

Author

Douglas B. Evans MD Chair, Professor in the Surgery department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Adenocarcinoma
Animals
Cell Growth Processes
Cell Line, Tumor
Cell Movement
Extracellular Signal-Regulated MAP Kinases
Humans
Male
Mice
Mice, Nude
Nerve Tissue Proteins
Neuropilin-1
Pancreatic Neoplasms
Phosphorylation
Protein Isoforms
Proto-Oncogene Proteins
Proto-Oncogene Proteins c-akt
RNA, Small Interfering
Receptors, Cell Surface
Semaphorin-3A
Up-Regulation
Vascular Endothelial Growth Factor A
Vascular Endothelial Growth Factor Receptor-2