Membrane‐Type Matrix Metalloproteinases 1 and 2 Exhibit Broad‐Spectrum Proteolytic Capacities Comparable to Many Matrix Metalloproteinases

TLDR

MT1‑MMP and MT2‑MMP are membrane‑bound enzymes that likely influence cell‑matrix interactions. The authors expressed soluble recombinant catalytic domains of MT1‑MMP and MT2‑MMP, including a MT1‑MMP variant containing both catalytic and hemopexin domains. The enzymes degraded a broad spectrum of extracellular matrix proteins—fibronectin, tenascin, nidogen, aggrecan, perlecan, and laminin (by MT2‑MMP)—and cleaved native type‑I and type‑III collagens into characteristic fragments (by MT1‑MMP with hemopexin), while also activating other MMPs and processing pro‑TNFα, but they did not degrade IL‑1β.

Abstract

Soluble proenzyme forms of the catalytic domains of membrane‐type matrix metalloproteinases 1 and 2 (MT1‐MMP and MT2‐MMP) and a form of MTI‐MMP containing the catalytic and hemopexin domains were expressed as soluble recombinant proteins. Purified, activated forms of the MT‐MMP were shown to degrade fibronectin, tenascin, nidogen, aggrecan and perlecan. Only MT2‐MMP showed activity against laminin. MT1‐MMP retaining the hemopexin domain was able to specifically cleave native type‐I and type‐III collagens into the 3/4‐1/4 fragments typical of the specific collagenases. The catalytic domain alone did not retain this activity. The MT‐MMP did not degrade interleukin‐1β, but, similarly to many other MMP, could process a pro [tumor necrosis factor (TNF) α] fusion protein to release mature TNF. However, the latter was subsequently degraded into smaller fragments. These results demonstrate that, in addition to their ability to activate other MMP, such as progelatinase A/proMMP2 and procollagenase‐3/proMMP13, MT‐MMP degrade a number of extracellular matrix macromolecules. Their location at the surface of cells implies that they could play a significant role in the modulation of cell‐matrix interactions.