Jin-Sae Rhee | Search PubMed

PubMed2002

RECKing MMP function: implications for cancer development.

Cancer is a multistage process requiring progressive genetic and epigenetic changes in neoplastic and responding stromal cells. Many alterations that occur during the process of malignant progression are regulated by the matrix metalloproteinase (MMP) family of extracellular proteases and their endogenous inhibitors. Recent work has identified a new cell-surface inhibitor of MMPs - RECK. RECK regulates MMP-induced pericellular signaling cascades during embryogenesis and tumorigenesis. Homozygous loss of RECK results in embryonic lethality and attenuated tumor development in adults - thus providing further support for an efficacious role for protease inhibitors as anticancer therapeutics.

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PubMed2002

Epithelial carcinogenesis: dynamic interplay between neoplastic cells and their microenvironment.

Matrix metalloproteinases (MMPs) have long been thought of as critical factors regulating matrix degradation associated with cell invasion into ectopic tissue compartments during primary tumor growth and metastasis. One member of the MMP family historically linked to these invasive processes is MMP-9/gelatinase B. By studying a transgenic mouse model of de novo epithelial carcinogenesis, new roles for MMP-9 have emerged that broaden the view of its functional contribution to malignant progression. The combined implication of these studies suggest that MMP-9 functionally contributes to cancer development; however, its major regulatory role may be in its ability to activate poorly diffusible and/or matrix-sequestered growth factors that regulate epithelial and/or endothelial cell growth as opposed to regulating cellular invasion across basement membranes.

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