Oral mucosal mesenchymal stem cell-derived exosomes: A potential therapeutic target in oral premalignant lesions
Oral mucosal mesenchymal stem cell-derived exosomes: A potential therapeutic target in oral premalignant lesions
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口腔粘膜间充质干细胞来源的外泌体：口腔癌前病变的潜在治疗靶点
DOI：
10.3892/ijo.2019.4756
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发表时间：
2019-05-01
影响因子：
5.2
通讯作者：
Liu, Hongwei
中科院分区：
文献类型：
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作者：
Li, Wenwen;Han, Ying;Liu, Hongwei
新的证据表明，间充质干细胞（MSC）在肿瘤微环境中起着不可或缺的作用。然而，MSC是否参与口腔癌的发生发展仍不清楚。本研究从临床组织中分离出MSC，并比较了正常口腔黏膜（N-MSC）、口腔白斑伴异型增生（LK-MSC）和口腔癌（Ca-MSC）来源MSC的差异。结果显示，LK-MSCs的增殖和迁移能力均低于N-MSCs和Ca-MSCs。此外，LK-MSC分泌的exosomes在体外具有显著的促增殖、促迁移和促侵袭作用，与Ca-MSC来源的exosomes相似。在3D共培养模型中也证明了促进作用。当外泌体的分泌被阻断时，LK-MSCs的促进作用被逆转。基于MSC衍生的外泌体的微阵列分析，microRNA-8485（miR-8485）被鉴定为异位表达。外泌体miR-8485能够促进肿瘤细胞的增殖、迁移和侵袭。因此，本研究强调了MSC衍生的外泌体和外泌体miR-8485在癌前病变和癌发生中的意义。干预MSC衍生的外泌体的分泌可能是延缓癌变的创新策略。
Emerging evidence indicates that mesenchymal stem cells (MSCs) serve an indispensable role in the tumor microenvironment. However, whether MSCs participate in the development of oral carcinogenesis remains unclear. The present study isolated MSCs from clinical tissues and investigated the differences of MSCs derived from normal oral mucosa (N-MSC), oral leukoplakia with dysplasia (LK-MSC) and oral carcinoma (Ca-MSC). The results revealed that the LK-MSCs exhibited reduced proliferation and migration, compared with the N-MSCs and Ca-MSCs. Furthermore, it was demonstrated that the exosomes secreted by LK-MSCs have significant roles in promoting proliferation, migration and invasion in vitro, which was similar to the Ca-MSC-derived exosomes. The promoting effect was also demonstrated in a 3D coculture model. When the secretion of exosomes was blocked, the promoting effect of LK-MSCs was reversed. Based on a microarray analysis of MSC-derived exosomes, microRNA-8485 (miR-8485) was identified to be ectopically expressed. The exosomal miR-8485 was capable of promoting the proliferation, migration and invasion of tumor cells. Therefore, the present study highlights the significance of MSC-derived exosomes and exosomal miR-8485 in premalignant lesions and carcinogenesis. Intervention with the secretion of MSC-derived-exosomes may be an innovative strategy to retard the carcinogenesis.