원문정보
초록
영어
The cell surface heparan sulfate proteoglycan syndecan-2 regulates the activation of matrix metalloproteinase-7 (MMP-7) as a docking receptor. Here, we demonstrate a novel role of MMP-7-mediated syndecan-2 shedding during cancer cell migration. Western blot analysis showed that shed syndecan-2 were found in the culture media from various colon cancer cells and the levels of shed syndecan-2 were elevated in that of HT-29 colon cancer cells overexpressing syndecan-2. MMP-7, but neither MMP-2 nor MMP-9, enhanced shedding of endogenous syndecan-2 in HT-29 cells, suggesting that MMP-7 mediates syndecan-2 shedding. Consistently, MMP-7 cleaved recombinant rat syndecan-2 at the N-terminal of Leu149 residue in the extracellular domain in vitro. The substitution of Asn148-Leu149 with Ser148-Ser149 significantly reduced MMP-7-mediated syndecan-2 shedding and subsequently syndecan-2-induced cancer cell migration. In addition, shed syndecan-2 ectodomain per sei enhanced colon cancer cell migration. Furthermore, overexpression of syndecan-2 enhanced migration and metastatic potential of mouse melanoma cells in mice, but this effect was diminished in non-cleavable syndecan-2 mutant. Taken together, these data suggest that MMP-7 mediates syndecan-2 shedding and shed syndecan-2 plays an important role in the regulation of colon cancer cell migration.