Laboratory of Tumor and Development Biology, GIGA-Cancer, University of Liège, Liège, Belgium.
Laboratory of Pharmaceutical Technology and Biopharmacy, CIRM, University of Liège, Liège, Belgium.
Cancer Lett. 2020 Dec 1;494:18-26. doi: 10.1016/j.canlet.2020.08.031. Epub 2020 Aug 28.
Emergence of novel therapeutic options in a perspective of personalized therapy of cancer relies on the discovery of precise molecular mechanisms involved in the switch from a localized tumor to invasive metastasis spread. Pro-tumor functions have been mostly ascribed to proteolytic enzymes from the metalloproteinase family including A Disintegrin And Metalloproteinases (ADAMs). Particularly, when expressed by cancer cells, ADAM28 protease supports cancer cell proliferation, survival and migration as well as metastatic progression. In sharp contrast, ADAM28 derived from the tumor microenvironment has shown to exert strong protective effects against deleterious metastasis dissemination. Indeed, depletion of host-derived ADAM28 (ADAM28 KO mice) accelerates colonization lung tissues, increases tumor foci implantation, and impairs T cell immune response. In this review, we outline specific ADAM28 functions when specifically expressed by carcinoma cells or by tumor microenvironment. Finally, we discuss about future research strategies that could be pursued to highlight new functions of this protease in cancer.
新型治疗选择在癌症个体化治疗中的出现依赖于对涉及从局部肿瘤到侵袭性转移扩散的精确分子机制的发现。肿瘤促进功能主要归因于金属蛋白酶家族的蛋白水解酶，包括解整合素和金属蛋白酶（ADAMs）。特别是，当在癌细胞中表达时，ADAM28 蛋白酶支持癌细胞增殖、存活和迁移以及转移进展。与此形成鲜明对比的是，源自肿瘤微环境的 ADAM28 已显示出对有害转移传播的强大保护作用。事实上，耗尽宿主来源的 ADAM28（ADAM28 KO 小鼠）会加速肺组织的定植，增加肿瘤灶的植入，并损害 T 细胞免疫反应。在这篇综述中，我们概述了当特定表达于癌细胞或肿瘤微环境时 ADAM28 的特定功能。最后，我们讨论了未来可以开展的研究策略，以强调这种蛋白酶在癌症中的新功能。
