Neuropilin-1 is Up-regulated by Cancer-associated Fibroblast-secreted IL-8 and Associated with Cell Proliferation of Gallbladder Cancer

Overview

Journal J Cell Mol Med

Specialties Cell Biology
Molecular Biology

Date 2020 Sep 20

PMID 32951327

Citations 8

Authors

Chen Chen

Rui Zhang

Li Ma

Qi Li

Ya-Ling Zhao

Guan-Jun Zhang

Dong Zhang

Wen-Zhi Li

Sheng Cao

Lin Wang

Zhi-Min Geng

Affiliations

Soon will be listed here.

Abstract

We previously demonstrated that cancer-associated fibroblasts (CAFs) promoted the proliferation of gallbladder cancer (GBC) cells, but the mechanism is not clear. Neuropilin-1 (NRP-1) plays an important role in various malignancies as transmembrane glycoprotein. Our goal was to reveal the relationship between CAFs and NRP-1 and their potential functions in GBC. In this study, we found NRP-1 was overexpressed in GBC tissue, associated with poor survival and was up-regulated by CAFs. The cytokine array cluster analysis revealed IL-8 secreted by CAFs facilitated the up-regulation of NRP-1 in tumour cells. NRP-1 knockdown suppressed tumour growth in vivo. Gene expression microarray analysis showed 581 differentially regulated genes under NRP-1 knockdown conditions. Ingenuity pathway analysis demonstrated that NRP-1 knockdown may inhibit tumour progression by affecting cell proliferation. We then confirmed that NRP-1 knockdown in NOZ and GBC-SD cells significantly inhibited cell proliferation. Additionally, the IL-8 mediated MDM2 and CCNA2 expression were affected by NRP-1 knockdown. Our findings suggested that NRP-1 was up-regulated by CAF-secreted IL-8, which subsequently promoted GBC cell proliferation, and these molecules may serve as useful prognostic biomarkers and therapeutic targets for GBC.

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