Department of Oral Medicine, Peking University School and Hospital of Stomatology, Beijing 100081, P.R. China.
Department of Stomatology, Beijing Hospital, Beijing 100730, P.R. China.
Int J Oncol. 2019 May;54(5):1567-1578. doi: 10.3892/ijo.2019.4756. Epub 2019 Mar 19.
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.
新出现的证据表明,间充质干细胞(MSCs)在肿瘤微环境中起着不可或缺的作用。然而,MSCs 是否参与口腔癌发生的发展尚不清楚。本研究从临床组织中分离出 MSCs,并研究了来自正常口腔黏膜(N-MSC)、口腔白斑伴异型增生(LK-MSC)和口腔癌(Ca-MSC)的 MSCs 的差异。结果表明,与 N-MSC 和 Ca-MSC 相比,LK-MSC 的增殖和迁移能力降低。此外,研究还表明,LK-MSC 分泌的外泌体在体外具有促进增殖、迁移和侵袭的显著作用,这与 Ca-MSC 衍生的外泌体相似。在 3D 共培养模型中也证明了这种促进作用。当阻断外泌体的分泌时,LK-MSC 的促进作用被逆转。基于 MSC 衍生外泌体的微阵列分析,鉴定出微小 RNA-8485(miR-8485)呈异位表达。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 在癌前病变和癌变中的重要性。干预 MSC 衍生外泌体的分泌可能是延缓癌变的一种创新策略。