Tumor exosome-mediated promotion of adhesion to mesothelial cells in gastric cancer cells.
Tumor exosome-mediated promotion of adhesion to mesothelial cells in gastric cancer cells.
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DOI：
10.18632/oncotarget.10869
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发表时间：
2016-08-30
期刊：
影响因子：
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通讯作者：
Otsuji E
中科院分区：
文献类型：
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作者：
Arita T;Ichikawa D;Konishi H;Komatsu S;Shiozaki A;Ogino S;Fujita Y;Hiramoto H;Hamada J;Shoda K;Kosuga T;Fujiwara H;Okamoto K;Otsuji E
腹膜转移由一系列高度复杂的步骤组成，并且潜在的分子机制的细节仍然很大程度上不清楚。在这项研究中，肿瘤来源的exosomes（TEX）的胃癌腹膜转移的进展的影响进行了研究。TEX在间皮细胞和胃癌细胞中均以细胞来源的非特异性方式内化。TEX内化到间皮细胞中促进间皮细胞与胃癌细胞之间的显著粘附，并且TEX内化到胃癌细胞中显著促进迁移能力，而间皮细胞来源的外泌体的内化没有。胃癌细胞系TEX和恶性胸腔积液TEX内化后，间皮细胞粘附相关分子如FN 1和LAMC 1的表达增加。用超离心法从细胞条件培养基中提取TEX。在粘附、侵袭和增殖试验中研究TEX对胃癌恶性潜能的影响。PCR阵列以及蛋白质印迹进行，以确定潜在的分子机制。恶性胸腔积液TEX内化后，间皮细胞的分子变化也得到了证实。TEX在胃癌腹膜转移过程中起重要作用，其机制可能与诱导间皮细胞粘附分子表达增加有关。
Peritoneal metastasis consists of a highly complex series of steps, and the details of the underlying molecular mechanism remain largely unclear. In this study, the effects of tumor-derived exosomes (TEX) on the progression of gastric cancers were investigated in peritoneal metastasis. TEX were internalized in both mesothelial and gastric cancer cells in a cellular origin non-specific manner. Internalization of TEX into mesothelial cells promoted significant adhesion between mesothelial and gastric cancer cells, and TEX internalization into gastric cancer cells significantly promoted migratory ability, while internalization of mesothelial cell-derived exosomes did not. Expression of adhesion-related molecules, such as fibronectin 1 (FN1) and laminin gamma 1 (LAMC1), were increased in mesothelial cells after internalization of TEX from gastric cancer cell line and malignant pleural effusion. TEX were extracted from cell-conditioned medium by ultracentrifugation. The effects of TEX on the malignant potential of gastric cancer were investigated in adhesion, invasion, and proliferation assays. PCR array as well as western blotting were performed to determine the underlying molecular mechanisms. The molecular changes in mesothelial cell after internalization of TEX derived from malignant pleural effusion were also confirmed. TEX may play a critical role in the development of peritoneal metastasis of gastric cancer, which may be partially due to inducing increased expression of adhesion molecules in mesothelial cells.