Roles of Matrix Metalloproteinase-9 in Cancer Metastasis

Abstract

Matrix metalloproteinases (MMPs), also called matrixins, function in the extracellular environment of cells and degrade both matrix and non-matrix proteins. They are multidomain proteins and their activities are regulated by tissue inhibitor of metalloproteinases (TIMPs). The uncontrolled regulation of MMPs is involved in various pathologic processes, such as tumor invasion, migration, host immune escape, extravasation, angiogenesis, and tumor growth. Especially, matrix metalloproteinase-9 (MMP-9) is one of the metastasis-accelerating genes involved in metastasis of various types of human cancers. Here, we review the member of MMP family and discusses their domain structure and function, enzyme activation, the mechanism of inhibition by TIMPs. In particular, we focus the role of MMP-9 in relation to cancer metastasis.

Salidroside, 8(E)-Nuezhenide, and Ligustroside from Ligustrum japonicum Fructus Inhibit Expressions of MMP-2 and -9 in HT 1080 Fibrosarcoma

“…MMP-2 and MMP-9 are proteolytic enzymes that degrade the extracellular matrix; they are closely related to the metastasis and invasion of tumors, and have long been regarded as attractive targets for the development of cancer therapeutics [ 27 , 28 , 29 ]. However, since most synthetic MMP inhibitors are toxic, the need for the development of more selective and newer pharmacophores of MMP inhibitors, without side effects, has been raised [ 12 , 14 ].…”