REGULATION OF MATRIX METALLOPROTEINASE-9 AND INHIBITION OF TUMOR INVASION BY THE MEMBRANE-ANCHORED GLYCOPROTEIN RECK

A human fibroblast cDNA expression library was screened for cDNA clone s giving rise to flat colonies when transfected into v-Ki-ras-transfor med NIH 3T3 cells. One such gene, RECK, encodes a membrane-anchored gl ycoprotein of about 110 kDa with multiple epidermal growth factor-like repeats and serine-protease inhibitor-like domains, While RECK mRNA i s expressed in various human tissues and untransformed cells, it is un detectable in tumor-derived cell lines and oncogenically transformed c ells. Restored expression of RECK in malignant cells resulted in suppr ession of invasive activity with concomitant decrease in the secretion of matrix metalloproteinase-9 (MMP-9), a key enzyme involved in tumor invasion and metastasis. Moreover, purified RECK protein was found to bind to, and inhibit the proteolytic activity of, MMP-9. Thus, RECK m ay link oncogenic signals to tumor invasion and metastasis.