This gene encodes an enzyme which degrades type IV collagen, the major structural component of basement membranes.

A complex of membrane type 1 MMP (MT1-MMP/MMP14) and tissue inhibitor of metalloproteinase 2 recruits pro-MMP 2 from the extracellular milieu to the cell surface.

Activity of MMP-2 relative to the other gelatinase (MMP-9) has been associated with severity of chronic airway diseases including Idiopathic interstitial pneumonia and Bronchiectasis.

In idiopathic interstitial pneumonia, MMP-2 activity was elevated in patients with the less severe disease phenotype which is more responsive and reversible with corticosteroid therapy.

[12] Disease-causing mutations in the MMP2 gene cause a rare type of skeletal dysplasia Multicentric Osteolysis, Nodulosis, and Arthropathy syndrome.

Increased MMP-2 activity has also been linked with a poor prognosis in multiple forms of cancer including colorectal, melanoma, breast, lung, ovarian, and prostate.

[20] As another example, cleavage of laminin-5, a component of the basement membrane, by MMP-2 has been shown to reveal a cryptic site inducing migration of breast epithelial cells.

[19] MMP-2 has also been shown to cleave other non-ECM substrates including growth factors such as TGF-β, FGF receptor-1, proTNF, IL-1β and various chemokines.

Localized MMP-2 activity plays an important role in endothelial cell migration, a key feature of angiogenesis.

Additionally, MMP-9 and other MMPs have been suggested to also play a complex, indirect role in angiogenesis by promoting VEGF mobilization and generating antiangiogenic factors.

[25] Finally, MMP-2 has been also shown to drive lymphangiogenesis, which is often excessive in tumor environments and can provide a route of metastasis for cancer cells.

Phase I clinical trials showed that MMP inhibitors are generally safe with minimal adverse side effects.

Additionally, trials with marimastat did show a slight increase in survival of patients with gastric or pancreatic cancer.

For example, cytotoxic agents or siRNA could be encapsulated in liposomes or viral vectors that become activated only upon proteolytic cleavage by a target MMP.