Disintegrin and metalloproteinase domain-containing protein 28 (ADAM28) (ADAM28)

Disintegrin and metalloproteinase domain-containing protein 28 (ADAM28) is a zinc-dependent enzyme that exists in two isoforms: a membrane-bound form (ADAM28m) and a shorter secreted form (ADAM28s) (UniProt Q9UKQ2). It is notably overexpressed in several malignancies, including non-small cell lung cancer and breast cancer, where it plays a critical role in tumor progression and metastasis (PubMed: 16452214). ADAM28 promotes tumor growth by cleaving insulin-like growth factor binding protein-3 (IGFBP-3), which releases IGF-I to stimulate cancer cell proliferation (PubMed: 16000603). Furthermore, it enhances the survival of circulating tumor cells by cleaving von Willebrand factor (vWF), thereby neutralizing vWF-mediated apoptosis (PubMed: 22564457). In the immune system, ADAM28 is involved in lymphocyte homing through its interaction with the alpha4beta1 integrin (PubMed: 11160608). Current therapeutic research focuses on developing monoclonal antibodies that specifically inhibit the proteolytic activity of ADAM28 to suppress tumor growth and metastatic spread (PubMed: 25351930).

Other names

ADAM metallopeptidase domain 28Metalloproteinase-like, disintegrin-like, and cysteine-rich protein-LMDC-LeMDC-L

Inhibition of the proteolytic activity of ADAM28 to prevent the cleavage of substrates such as IGFBP-3 and von Willebrand factor, thereby inhibiting tumor cell proliferation and metastasis.