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外泌体来源的ADAM17促进结直肠癌肝转移

Exosome-Derived ADAM17 Promotes Liver Metastasis in Colorectal Cancer.

作者信息

Sun Jinbing, Lu Zhihua, Fu Wei, Lu Kuangyi, Gu Xiuwen, Xu Feng, Dai Jiamin, Yang Yang, Jiang Jianlong

机构信息

Department of General Surgery, Changshu No. 1 People's Hospital, Affiliated Changshu Hospital of Soochow University, Changshu, China.

Department of Radiology, Changshu No. 1 People's Hospital, Affiliated Changshu Hospital of Soochow University, Changshu, China.

出版信息

Front Pharmacol. 2021 Sep 23;12:734351. doi: 10.3389/fphar.2021.734351. eCollection 2021.

Abstract

Exosomes derived from cancer cells are deemed important drivers of pre-metastatic niche formation at distant organs, but the underlying mechanisms of their effects remain largely unknow. Although the role of ADAM17 in cancer cells has been well studied, the secreted ADAM17 effects transported via exosomes are less understood. Herein, we show that the level of exosome-derived ADAM17 is elevated in the serum of patients with metastatic colorectal cancer as well as in metastatic colorectal cancer cells. Furthermore, exosomal ADAM17 was shown to promote the migratory ability of colorectal cancer cells by cleaving the E-cadherin junction. Moreover, exosomal ADAM17 overexpression as well as RNA interference results highlighted its function as a tumor metastasis-promoting factor in colorectal cancer and . Taken together, our current work suggests that exosomal ADAM17 is involved in pre-metastatic niche formation and may be utilized as a blood-based biomarker of colorectal cancer metastasis.

摘要

源自癌细胞的外泌体被认为是远处器官转移前生态位形成的重要驱动因素,但其作用的潜在机制仍 largely unknow。虽然ADAM17在癌细胞中的作用已得到充分研究,但通过外泌体运输的分泌型ADAM17的作用了解较少。在此,我们表明,转移性结直肠癌患者血清以及转移性结直肠癌细胞中外泌体来源的ADAM17水平升高。此外,外泌体ADAM17通过切割E-钙粘蛋白连接促进结直肠癌细胞的迁移能力。此外,外泌体ADAM17的过表达以及RNA干扰结果突出了其作为结直肠癌肿瘤转移促进因子的功能。综上所述,我们目前的工作表明,外泌体ADAM17参与转移前生态位的形成,可能用作结直肠癌转移的血液生物标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d2e1/8506248/980245f3da8e/fphar-12-734351-g001.jpg

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