ADAM metallopeptidase with thrombospondin type 1 motif 15 (ADAMTS15)

ADAM metallopeptidase with thrombospondin type 1 motif 15 (ADAMTS15) is an extracellular zinc-dependent metalloprotease of the ADAMTS family, characterized by a multi-domain structure including a metalloproteinase, disintegrin-like, and multiple thrombospondin type 1 repeats[1][3]. It catalyzes the proteolytic cleavage of extracellular matrix proteoglycans, notably versican and aggrecan, facilitating tissue remodeling in development (skeletal, cardiovascular, and musculoskeletal systems) and in adult tissue repair[1][2][3]. ADAMTS15 has been implicated as a tumor suppressor, with loss or reduction of its expression correlated with increased cancer invasion, progression, and poor prognosis in breast, colon, ovarian, and prostate cancers, likely due to its role in remodeling the tumor microenvironment[2][3]. Dysregulation of ADAMTS15 is also linked to musculoskeletal and cardiovascular diseases, highlighting a potential but still largely unexploited therapeutic target for ECM-related pathologies. Knockout and mechanistic studies suggest embryonic and tissue-selective expression, but functional redundancy with related ADAMTS proteases and a lack of specific inhibitors limit clinical translation so far[2][3][1].

Other names

A disintegrin and metalloproteinase with thrombospondin motifs 15ADAM-TS 15ADAM-TS15ADAMTS-15DA12Metalloprotease disintegrin 15 with thrombospondin domainsPreproprotein ADAMTS15

Therapeutic mechanisms (experimental): inhibition of proteolytic activity could prevent excessive extracellular matrix degradation, relevant to arthritis and cancer progression[2]. Potential tumor suppressor: loss-of-function/epigenetic silencing is linked to tumor progression in some cancer types[2][3].