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Neuropilin-1 is up-regulated by cancer-associated fibroblast-secreted IL-8 and associated with cell proliferation of gallbladder cancer
- Source :
- Journal of Cellular and Molecular Medicine
- Publication Year :
- 2019
-
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.
- Subjects :
- 0301 basic medicine
Male
medicine.medical_treatment
Mice, Nude
gallbladder cancer
03 medical and health sciences
0302 clinical medicine
Downregulation and upregulation
Cancer-Associated Fibroblasts
Cell Line, Tumor
Neuropilin 1
medicine
Cholecystitis
Animals
Humans
Interleukin 8
RNA, Small Interfering
prognostic factor
Tumor Stem Cell Assay
Cell Proliferation
Oligonucleotide Array Sequence Analysis
Gene knockdown
cancer‐associated fibroblasts
biology
Cell growth
Interleukin-8
Cell Biology
Original Articles
Middle Aged
Prognosis
Survival Analysis
Neuropilin-1
Up-Regulation
Gene Expression Regulation, Neoplastic
030104 developmental biology
Cytokine
030220 oncology & carcinogenesis
Multivariate Analysis
Cancer research
biology.protein
Molecular Medicine
Mdm2
Female
Gallbladder Neoplasms
Original Article
neuropilin‐1
Subjects
Details
- ISSN :
- 15824934
- Volume :
- 24
- Issue :
- 21
- Database :
- OpenAIRE
- Journal :
- Journal of cellular and molecular medicine
- Accession number :
- edsair.doi.dedup.....ef6d6ce4fd5582d1eaaaabb17c0b7013