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肺癌相关间充质干细胞通过诱导上皮-间质转化和干细胞样重编程促进肿瘤转移和肿瘤发生。

Lung cancer-associated mesenchymal stem cells promote tumor metastasis and tumorigenesis by induction of epithelial-mesenchymal transition and stem-like reprogram.

作者信息

Yan Cihui, Chang Jingjing, Song Xinmiao, Qi Ying, Ji Zhenyu, Liu Ting, Yu Wenwen, Wei Feng, Yang Lili, Ren Xiubao

机构信息

Department of Immunology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center of Cancer, Key Laboratory of Cancer Prevention and Therapy, Ti-Yuan-Bei, He Xi 300060, Tianjin, China.

Department of Electromyogram, 3rd Affiliated Hospital of Hebei Medical University, Shijiazhuang 050051, Hebei, China.

出版信息

Aging (Albany NY). 2021 Mar 19;13(7):9780-9800. doi: 10.18632/aging.202732.

Abstract

Mesenchymal stem cells (MSCs) have attracted more attention in antitumor therapy by using MSCs as vehicles or targeting modulators of MSCs. But their role and mechanisms in tumor progression are less known. In the present study, we successfully isolated pairs of MSCs from lung cancer (LC-MSCs) and adjacent tumor-free tissues. Based on the coculture system and animal studies , we originally found that LC-MSCs significantly promoted tumor metastasis and tumorigenesis both and . Partial epithelial-mesenchymal transition (EMT) was induced in lung cancer cells by LC-MSCs by the evidence of remarkable increase in snail and slug expression but not in other EMT-associated genes. The expression of stem related genes also escalated significantly. And spheroids perfectly formed when tumor cells were co-incubated with LC-MSCs. These results revealed a close link of partial EMT and acquisition of stem-like traits in lung cancer cells which was induced by LC-MSCs and greatly promoted metastasis and tumorigenesis in lung cancer. Our findings provided a new insight into LC-MSCs in tumor progression and helped to identify LC-MSCs as a potential vehicle or target for lung cancer therapy.

摘要

间充质干细胞(MSCs)通过作为载体或靶向调节剂在抗肿瘤治疗中受到了更多关注。但它们在肿瘤进展中的作用和机制尚不清楚。在本研究中,我们成功地从肺癌组织(LC-MSCs)和相邻的无肿瘤组织中分离出成对的间充质干细胞。基于共培养系统和动物研究,我们首次发现LC-MSCs显著促进肿瘤转移和肿瘤发生。通过蜗牛和蛞蝓表达显著增加的证据表明,LC-MSCs诱导肺癌细胞发生部分上皮-间质转化(EMT),但其他与EMT相关的基因未出现这种情况。干细胞相关基因的表达也显著升高。当肿瘤细胞与LC-MSCs共同孵育时,球体完美形成。这些结果揭示了LC-MSCs诱导的肺癌细胞部分EMT与获得干细胞样特性之间的紧密联系,这极大地促进了肺癌的转移和肿瘤发生。我们的研究结果为LC-MSCs在肿瘤进展中的作用提供了新的见解,并有助于将LC-MSCs鉴定为肺癌治疗的潜在载体或靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/42c1/8064219/11c98d7f05e2/aging-13-202732-g001.jpg

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