Matrix metalloproteinase-1 contribution to sarcoma cell invasion.
Bottom Line: Inhibition of prenylation by farnesyl transferase inhibitor (FTI-276) decreased extracellular MMP-1 and subsequently reduced invasiveness by 30%.MMP-1 directional delivery to these structures were confirmed by combination of a MMP-1-specific fluorogenic substrate, a MMP1-Ds-Red fusion protein construct expression and DQ-collagen degradation, which demonstrated coupling of directional delivery and activation.These results indicate that MMP-1 directional delivery to podia structures is involved in the invasive activity of sarcoma cells, and this process is prenylation sensitive.
Affiliation: Sarcoma Biology Laboratory of Sylvester Comprehensive Cancer Center, University of Miami, Miller School of Medicine, FL, USA. firstname.lastname@example.orgShow MeSH
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Mentions: General paradigm is that MMP-1 secreted and deposited in the extracellular matrix as an inactive zymogen by various cell types where it is subsequently activated . To investigate further if MMP-1 cellular production and localization can overlap with the underlying collagen matrix degradation beneath the cells, live cell fluorescent imaging in combination with DQ-collagen, MMP1-DsRed fusion protein expression and MMP-1 cleavage specific Fluorogenic Substrate-III (Fig. 4A and B; Refs. [48, 49]) were used in invadopodia assays.
Affiliation: Sarcoma Biology Laboratory of Sylvester Comprehensive Cancer Center, University of Miami, Miller School of Medicine, FL, USA. email@example.com