Skip to main content

ORIGINAL RESEARCH article

Front. Immunol.
Sec. Cancer Immunity and Immunotherapy
Volume 15 - 2024 | doi: 10.3389/fimmu.2024.1434027
This article is part of the Research Topic Community Series in Adenosine Pathways in Cancer Immunity and Immunotherapy: Volume II View all 3 articles

A disintegrin and metalloproteinase domain 10 (ADAM10) expression inhibition by the small molecules adenosine, cordycepin and N6, N6-dimethyladenosine and immune regulation in malignant cancers

Provisionally accepted
Wenqian Zhang Wenqian Zhang 1Fu Jiewen Fu Jiewen 1Jiaman Du Jiaman Du 1Xiaoyan Liu Xiaoyan Liu 1Cheng Jingliang Cheng Jingliang 1Chunli Wei Chunli Wei 1Youhua Xu Youhua Xu 2*Junjiang Fu Junjiang Fu 1*
  • 1 Research Center for Preclinical Medicine, Southwest Medical University, Luzhou, China
  • 2 Macau University of Science and Technology, Taipa, Macao, Macao, SAR China

The final, formatted version of the article will be published soon.

    A disintegrin and metalloproteinase domain 10 (ADAM10), a member of the ADAM family, is a cellular surface protein with potential adhesion and protease / convertase functions. The expression regulations in cancers by natural products [adenosine (AD) and its analogs, cordycepin (CD), and N6, N6-dimethyladenosine (m62A)], and immune regulation are unclear. As results, AD, CD, and m62A inhibited ADAM10 expression in various cancer cell lines, indicating their roles in anti-cancer agents. Further molecular docking with ADAM10 protein found the binding energies of all docking groups were <-7 kcal/mol for all small-molecules (AD, CD and m62A), suggesting very good binding activities. In addition, analysis of the immunomodulatory roles in cancer showed that ADAM10 was negatively correlated with immunomodulatory genes such as CCL27, CCL14, CCL25, CXCR5, HLA-B, HLA-DOB1, LAG3, TNFRSF18, and TNFRSF4 in bladder urothelial carcinoma, thymoma, breast invasive carcinoma, TGCT, kidney renal papillary cell carcinoma, SKCM and thyroid carcinoma, indicating the immune-promoting roles for ADAM10. LAG3 mRNA levels were reduced by both AD and CD in vivo. ADAM10 is also negatively associated with tumor immunosuppression and interrelated with the immune infiltration of tumors. Overall, the present study determined ADAM10 expression by AD, CD and m62A, and in AD or CD/ADAM10/LAG3 signaling in cancers, and suggested a potential method for immunotherapy of cancers by targeting ADAM10 using the small molecules AD, CD and m62A.

    Keywords: ADAM10, Expression, Pan-cancer, Immunotherapy, Adenosine, Cd, m 6 2A

    Received: 17 May 2024; Accepted: 29 Jul 2024.

    Copyright: © 2024 Zhang, Jiewen, Du, Liu, Jingliang, Wei, Xu and Fu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence:
    Youhua Xu, Macau University of Science and Technology, Taipa, Macao, Macao, SAR China
    Junjiang Fu, Research Center for Preclinical Medicine, Southwest Medical University, Luzhou, China

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.