Regulation of the Mr 72,000 Type IV Collagenase by the Type I Insulin-like Growth Factor Receptor

摘要: The Mr 72,000 type IV collagenase [matrix metalloproteinase 2 (MMP-2)] is known to play a central role in the process of invasion and metastasis, but its regulation not clearly understood. We investigated I insulin-like growth factor (IGF-I) tumor cell synthesis MMP-2. Highly invasive murine Lewis lung carcinoma subline H-59 cells, which expression IGF-I receptor (IGF-IR) was blocked by antisense mRNA, had significantly reduced reconstituted basement membrane (Matrigel) as compared with that controls. These cells decrease up 6-fold level MMP-2 mRNA transcripts, assessed reverse transcription-PCR, corresponding reduction protein synthesis, Western blot assay gelatin zymography. Conversely, overexpression IGF-IR second, poorly (M-27) low endogenous levels increased 7.5- 4-fold, respectively. Ligand-mediated activation induced both types. results identify regulator cellular invasion.