ADAM8 (F3G9R) Rabbit mAb #88034

A disintegrin and metalloprotease (ADAM) family of multidomain membrane proteins influences cell signaling and adhesion by shedding cell surface proteins, such as cytokines and growth factors, influencing cell adhesion to the extracellular matrix (ECM), and directly remodeling the ECM. Conserved domains in ADAM family members include a prodomain, a zinc-dependent metalloprotease domain, a disintegrin domain, a cysteine-rich domain, an EGF-like sequence, and a short cytoplasmic tail. The prodomain is thought to aid in protein folding, and disintegrin and cysteine-rich domains mediate adhesion through binding (at least in part) to integrins. Phosphorylation of the cytoplasmic tail and its interaction with other signaling proteins may influence intra- and extracellular signaling (1,2).

ADAM8 is unique among family members in its relatively broad expression across various immune cells, including monocytes, macrophages, neutrophils, eosinophils, dendritic cells, and lymphocytes, as well as in epithelial cells in various tissues. ADAM8 is generally expressed at low levels in normal adult tissues but is significantly upregulated in response to inflammatory stimuli and various pathological conditions. ADAM8 is aberrantly overexpressed in numerous cancer types and is increasingly recognized as a prognostic biomarker and therapeutic target. High expression of ADAM8 in breast cancer, particularly in triple-negative breast cancer (TNBC), has been shown to correlate with aggressive phenotype, tumor growth, dissemination, and metastasis, and poor patient outcome. In this tumor type, it is thought to influence cell motility and interaction with the extracellular matrix. ADAM8 is highly expressed in glioblastoma (GBM) tumors, specifically within the tumor environment where it is thought to affect intracellular kinase (e.g., STAT3, MAPK, PI3K/Akt) signaling, and promote angiogenesis, thereby enhancing chemoresistance. Upregulation of ADAM8 is also associated with increased migration and invasiveness of cancer cells in pancreatic tumors, and correlates with reduced survival. ADAM8 expression is found in hepatocellular carcinoma and is associated with tumor size, differentiation, recurrence, metastasis, and poor prognosis. It can promote proliferation, migration, and invasion of hepatoma cells. Upregulation of ADAM8 is also observed in colon cancer, where it is thought to promote invasion by inducing epithelial-mesenchymal transition (EMT) via the TGF-β/Smad2/3 signaling pathway. Lastly, overexpression of ADAM8 is associated with lung cancer progression (3-7).