Barnieh Francis M, Galuska Sebastian P, Loadman Paul M, Ward Simon, Falconer Robert A, El-Khamisy Sherif F
Institute of Cancer Therapeutics, Faculty of Life Sciences, University of Bradford, Bradford BD7 1DP, UK.
Institute for Reproductive Biology, Research Institute for Farm Animal Biology (FBN), Wilhelm-Stahl-Allee 2, Dummerstorf, Germany.
iScience. 2023 Oct 16;26(11):108219. doi: 10.1016/j.isci.2023.108219. eCollection 2023 Nov 17.
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.
利用癌症组织与非癌症组织之间的差异为抗癌药物的选择性靶向提供了新的机会。CD13是一种高度糖基化的蛋白质，是癌症药物发现中具有重大未满足临床潜力的一个例子。尽管CD13在癌症中高表达且具有活性，但它也在许多正常组织中表达。在此，我们报告了CD13在不同组织中的差异组织糖基化，并首次证明临床前癌症组织中CD13的糖基化性质和模式与正常组织不同。我们鉴定出CD13的癌症特异性O-糖基化，它在癌症模型中选择性地阻断其检测，但在正常组织中则不会。此外，观察到癌症表达的CD13的代谢活性严重依赖于其独特的糖基化。因此，我们的数据证明了离散的癌症特异性CD13糖型的存在，并提出癌症特异性CD13糖型作为有效癌症靶向治疗的临床有用靶点。
