ADAM8, also known as CD156a, is a member of the A Disintegrin And Metalloproteinase (ADAM) family. It has proteolytic and non-proteolytic functions, such as ectodomain shedding of extracellular and membrane proteins, and binding to integrins to activate signaling pathways. It is involved in cell-cell communication, and is expressed mainly in immune system cells, tumor cells, and is associated with multiple biological processes like inflammation, angiogenesis, and metastasis [1,3,5].

In cancer, high ADAM8 expression levels are linked to invasiveness and poor patient outcomes in malignancies like breast, pancreatic, and brain cancer. It promotes cancer progression via proteolytic degradation of extracellular matrix components, cleavage of cell surface proteins, and activation of integrin-related signaling pathways [1]. In macrophages, ADAM8 deficiency promotes cardiac repair after myocardial infarction. Macrophage-specific ADAM8 knockout (KO) mice showed enhanced angiogenesis, suppressed inflammation, and improved cardiac function. Mechanistically, ADAM8 binds to ANXA2, and its deficiency activates autophagy through the ANXA2-mTOR-autophagy axis [2]. In acute respiratory distress syndrome (ARDS), Adam8-/-mice had impaired neutrophil transmigration, and both genetic deletion and pharmacologic inhibition of ADAM8 attenuated neutrophil infiltration and lung injury [4].

In summary, ADAM8 is a multifunctional protein involved in inflammation, cancer, and cardiovascular processes. KO mouse models have revealed its role in promoting cancer progression, inhibiting cardiac repair post-myocardial infarction, and driving neutrophil migration in ARDS. These findings suggest ADAM8 could be a potential therapeutic target in these disease areas.

References:

1. Conrad, Catharina, Benzel, Julia, Dorzweiler, Kristina, Nimsky, Christopher, Bartsch, Jörg W. 2019. ADAM8 in invasive cancers: links to tumor progression, metastasis, and chemoresistance. In Clinical science (London, England : 1979), 133, 83-99. doi:10.1042/CS20180906. https://pubmed.ncbi.nlm.nih.gov/30635388/

2. Ji, Zhenjun, Guo, Jiaqi, Zhang, Rui, Yao, Yuyu, Ma, Genshan. 2024. ADAM8 deficiency in macrophages promotes cardiac repair after myocardial infarction via ANXA2-mTOR-autophagy pathway. In Journal of advanced research, , . doi:10.1016/j.jare.2024.07.037. https://pubmed.ncbi.nlm.nih.gov/39097092/

3. Matsuno, Osamu, Kumamoto, Toshihide, Higuchi, Yasunori. . ADAM8 in allergy. In Inflammation & allergy drug targets, 7, 108-12. doi:. https://pubmed.ncbi.nlm.nih.gov/18691140/

4. Conrad, Catharina, Yildiz, Daniela, Cleary, Simon J, Looney, Mark R, Bartsch, Jörg W. 2022. ADAM8 signaling drives neutrophil migration and ARDS severity. In JCI insight, 7, . doi:10.1172/jci.insight.149870. https://pubmed.ncbi.nlm.nih.gov/35132956/

5. Cook, Lena, Gharzia, Federico Guillermo, Bartsch, Jörg W, Yildiz, Daniela. 2023. A jack of all trades - ADAM8 as a signaling hub in inflammation and cancer. In The FEBS journal, 291, 3989-4008. doi:10.1111/febs.17034. https://pubmed.ncbi.nlm.nih.gov/38097912/