Cancer-specific glycosylation of CD13 impacts its detection and activity in preclinical cancer tissues.
| Autor: | Barnieh FM; Institute of Cancer Therapeutics, Faculty of Life Sciences, University of Bradford, Bradford BD7 1DP, UK., Galuska SP; Institute for Reproductive Biology, Research Institute for Farm Animal Biology (FBN), Wilhelm-Stahl-Allee 2, Dummerstorf, Germany., Loadman PM; Institute of Cancer Therapeutics, Faculty of Life Sciences, University of Bradford, Bradford BD7 1DP, UK., Ward S; Incanthera plc, Manchester M2 4NH, UK., Falconer RA; Institute of Cancer Therapeutics, Faculty of Life Sciences, University of Bradford, Bradford BD7 1DP, UK., El-Khamisy SF; Institute of Cancer Therapeutics, Faculty of Life Sciences, University of Bradford, Bradford BD7 1DP, UK. |
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| Jazyk: | angličtina |
| Zdroj: | IScience [iScience] 2023 Oct 16; Vol. 26 (11), pp. 108219. Date of Electronic Publication: 2023 Oct 16 (Print Publication: 2023). |
| DOI: | 10.1016/j.isci.2023.108219 |
| Abstrakt: | Harnessing the differences between cancer and non-cancer tissues presents new opportunities for selective targeting by anti-cancer drugs. CD13, a heavily glycosylated protein, is one example with significant unmet clinical potential in cancer drug discovery. Despite its high expression and activity in cancers, CD13 is also expressed in many normal tissues. Here, we report differential tissue glycosylation of CD13 across tissues and demonstrate for the first time that the nature and pattern of glycosylation of CD13 in preclinical cancer tissues are distinct compared to normal tissues. We identify cancer-specific O-glycosylation of CD13, which selectively blocks its detection in cancer models but not in normal tissues. In addition, the metabolism activity of cancer-expressed CD13 was observed to be critically dependent on its unique glycosylation. Thus, our data demonstrate the existence of discrete cancer-specific CD13 glycoforms and propose cancer-specific CD13 glycoforms as a clinically useful target for effective cancer-targeted therapy. Competing Interests: The authors declare no competing interests. (© 2023 The Authors.) |
| Databáze: | MEDLINE |
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