Biological Sciences Platform, Sunnybrook Research Institute, Toronto, Canada.
Department of Medical Biophysics, University of Toronto, Canada.
FEBS J. 2019 Sep;286(17):3299-3332. doi: 10.1111/febs.14985. Epub 2019 Jul 29.
The C-type lectin domain (CTLD) group 14 family of transmembrane glycoproteins consist of thrombomodulin, CD93, CLEC14A and CD248 (endosialin or tumour endothelial marker-1). These cell surface proteins exhibit similar ectodomain architecture and yet mediate a diverse range of cellular functions, including but not restricted to angiogenesis, inflammation and cell adhesion. Thrombomodulin, CD93 and CLEC14A can be expressed by endothelial cells, whereas CD248 is expressed by vasculature associated pericytes, activated fibroblasts and tumour cells among other cell types. In this article, we review the current literature of these family members including their expression profiles, interacting partners, as well as established and speculated functions. We focus primarily on their roles in the vasculature and inflammation as well as their contributions to tumour immunology. The CTLD group 14 family shares several characteristic features including their ability to be proteolytically cleaved and engagement of some shared extracellular matrix ligands. Each family member has strong links to tumour development and in particular CD93, CLEC14A and CD248 have been proposed as attractive candidate targets for cancer therapy.
C 型凝集素结构域（CTLD）第 14 家族跨膜糖蛋白包括血栓调节蛋白、CD93、CLEC14A 和 CD248（内皮细胞唾液酸糖蛋白或肿瘤内皮标志物-1）。这些细胞表面蛋白具有相似的胞外结构域结构，但介导多种不同的细胞功能，包括但不限于血管生成、炎症和细胞黏附。血栓调节蛋白、CD93 和 CLEC14A 可由内皮细胞表达，而 CD248 则由与血管相关的周细胞、激活的成纤维细胞和肿瘤细胞等其他细胞类型表达。在本文中，我们回顾了这些家族成员的现有文献，包括它们的表达谱、相互作用伙伴以及已建立和推测的功能。我们主要关注它们在血管和炎症中的作用以及它们对肿瘤免疫学的贡献。CTLD 第 14 家族具有几个共同的特征，包括能够被蛋白水解切割和结合一些共同的细胞外基质配体。每个家族成员都与肿瘤的发生发展密切相关，特别是 CD93、CLEC14A 和 CD248 已被提议作为癌症治疗的有吸引力的候选靶点。
