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. 2005 Aug 19;94(7):569–574. doi: 10.1111/j.1349-7006.2003.tb01484.x

Roles of pericellular proteolysis by membrane type‐1 matrix metalloproteinase in cancer invasion and angiogenesis

Motoharu Seiki 1,✉, Ikuo Yana 1
PMCID: PMC11160244  PMID: 12841863

Abstract

Behavior of cancer cells is profoundly affected by their microenvironment, which is often controlled by pericellular proteolysis or the processing of protein components, including extracellular matrices, growth factors, cytokines, receptors, cell adhesion molecules, and so on. Matrix metalloproteinases (MMPs) are a family of zinc‐dependent proteases responsible for the proteolytic events in the extracellular milieu. Among the multiple MMPs expressed in a wide range of tumors, membrane type‐1 MMP (MT1‐MMP), which is expressed especially in tumor cells with significant invasive properties, is thought to be particularly important for pericellular proteolysis. Recent studies have elucidated in part how MT1‐MMP is regulated biologically for the promotion of invasion by tumors or for angiogenesis by endothelial cells. Understanding of the proteolysis by, and the regulation of MT1‐MMP, which probably promotes cell invasion, could provide a therapeutic hint as to how to block or delay the progression of cancer.

Abbreviations:

APC

adenomatous polyposis coli

uPAR, urokinase

urokinase‐type plasminogen activator receptor

Tcf4

transcription factor 4

Wnt

wingless‐type MMTV integration

HGF

hepatocyte growth factor

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