Elimination of LMP1-expressing cells from a monolayer of gastric cancer AGS cells
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Yoshitaka Sato1, Shingo Ochiai1, Takayuki Murata1, Teru Kanda2, Fumi Goshima1 and Hiroshi Kimura1
1Department of Virology, Nagoya University Graduate School of Medicine, Showa-Ku, Nagoya 466-8550, Japan
2Division of Microbiology, Faculty of Medicine, Tohoku Medical and Pharmaceutical University, Aoba-Ku, Sendai 981-8558, Japan
Hiroshi Kimura, email: [email protected]
Keywords: EBV, LMP1, cell competition, cell-cell communication, gastric cancer
Received: July 06, 2016 Accepted: March 28, 2017 Published: April 10, 2017
Epstein-Barr virus (EBV) latently infects malignant epithelial cells in approximately 10% of all gastric cancers. Latent membrane protein 1 (LMP1), an oncogenic protein, plays an important role in malignant transformation in EBV-associated nasopharyngeal carcinoma and B-cell lymphoma; however, its expression has not been detected in EBV-associated gastric cancer. To address why LMP1 has not been detected in EBV-positive gastric tumors, we focused on the interactions between LMP1-positive and -negative cells and stably expressed LMP1 in the gastric cancer cell line AGS. We showed that the number of LMP1-positive cells decreased gradually with each cell passage when the cells were co-cultured with LMP1-negative cells. Time-lapse imaging showed that LMP1-positive cells were eliminated from a monolayer of LMP1-negative cells. Furthermore, LMP1-positive cells stimulated the proliferation of surrounding LMP1-negative cells, but not LMP1-positive cells, via exosome-mediated EGFR activation. Our data indicate that LMP1 expression drives cell competition between LMP1-positive and -negative cells, affecting the behavior of the cells within gastric tissue.
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