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.
Keywords: EBV; LMP1; cell competition; cell-cell communication; gastric cancer.