Regulation of proliferation and invasion by the IGF signalling pathway in Epstein-Barr virus-positive gastric cancer

Jeong, Inhye; Kang, Sun Kyoung; Kwon, Woo Sun; Kim, Hyun Jeong; Kim, Kyoo Hyun; Kim, Hyun Myong; Lee, Andre; Lee, Suk Kyeong; Bogenrieder, Thomas; Chung, Hyun Cheol and Rha, Sun Young (2018): Regulation of proliferation and invasion by the IGF signalling pathway in Epstein-Barr virus-positive gastric cancer. In: Journal of Cellular and Molecular Medicine, Vol. 22, No. 12: pp. 5899-5908

Abstract

Several carcinomas including gastric cancer have been reported to contain Epstein-Barr virus (EBV) infection. EBV-associated gastric cancer (EBVaGC) is classified as one of four molecular subtypes of gastric cancer by The Cancer Genome Atlas (TCGA) group with increased immune-related signatures. Identification of EBV-dependent pathways with significant biological roles is needed for EBVaGC. To compare the biological changes between AGS gastric epithelial cells and EBV-infected AGS (AGS-EBV) cells, proliferation assay, CCK-8 assay, invasion assay, cell cycle analysis, RT-PCR, Western blot and ELISA were performed. BI836845, a humanized insulin-like growth factor (IGF) ligand-neutralizing antibody, was used for IGF-related signalling pathway inhibition. AGS-EBV cells showed slower proliferating rate and higher sensitivity to BI836845 compared to AGS cells. Moreover, invasiveness of AGS-EBV was increased than that of AGS, and BI836845 treatment significantly decreased the invasiveness of AGS-EBV. Although no apoptosis was detected, entry into the S phase of the cell cycle was delayed in BI836845-treated AGS-EBV cells. In conclusion, AGS-EBV cells seem to modulate their proliferation and invasion through the IGF signalling pathway. Inhibition of the IGF signalling pathway therefore could be a potential therapeutic strategy for EBVaGC.

• Item Type: Journal article
• Faculties: Medicine
• Subjects: 600 Technology > 610 Medicine and health
• ISSN: 1582-4934
• Language: English