Elimination of LMP1-expressing cells from a monolayer of gastric cancer AGS cells.
Elimination of LMP1-expressing cells from a monolayer of gastric cancer AGS cells.
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DOI：
10.18632/oncotarget.16996
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发表时间：
2017-06-13
期刊：
影响因子：
--
通讯作者：
Kimura H
中科院分区：
文献类型：
--
作者：
Sato Y;Ochiai S;Murata T;Kanda T;Goshima F;Kimura H
EB病毒（EBV）潜伏感染约10%的胃癌中的恶性上皮细胞。潜伏膜蛋白1（LMP1）是一种致癌蛋白，在EBV相关的鼻咽癌和B细胞淋巴瘤的恶性转化中起重要作用，但在EBV相关的胃癌中未见表达。为了解决为什么LMP1尚未检测到EBV阳性胃肿瘤，我们专注于LMP1阳性和阴性细胞之间的相互作用和稳定表达的LMP1在胃癌细胞系AGS。我们发现，当细胞与LMP1阴性细胞共培养时，LMP1阳性细胞的数量随着每代细胞的传代而逐渐减少。延时成像显示LMP1阳性细胞从单层LMP1阴性细胞中消除。此外，LMP1阳性细胞通过外泌体介导的EGFR活化刺激周围LMP1阴性细胞的增殖，但不刺激LMP1阳性细胞的增殖。我们的数据表明，LMP1表达驱动LMP1阳性和阴性细胞之间的细胞竞争，影响胃组织内细胞的行为。
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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