The matrix metalloproteinase-7 regulates the extracellular shedding of syndecan-2 from colon cancer cells

Biochem Biophys Res Commun. 2012 Jan 27;417(4):1260-4. doi: 10.1016/j.bbrc.2011.12.120. Epub 2011 Dec 29.

Abstract

The cell surface heparan sulfate proteoglycan syndecan-2 regulates the activation of matrix metalloproteinase-7 (MMP-7) as a docking receptor. Here, we demonstrate the role of MMP-7 on syndecan-2 shedding in colon cancer cells. Western blot analysis showed that shed syndecan-2 was found in the culture media from various colon cancer cells. Overexpression of MMP-7 enhanced syndecan-2 shedding, whereas the opposite was true when MMP-7 levels were knocked-down using small inhibitory RNAs. Consistently, HT29 cells treated with MMP-7, but neither MMP-2 nor MMP-9, showed increased shed syndecan-2 in a time- and concentration-dependent manner. Furthermore, MALDI-TOF MS analysis and N-terminal amino acid sequencing revealed that MMP-7 cleaved both recombinant syndecan-2 and an endogenously glycosylated syndecan-2 ectodomain in the N-terminus at Leu(149) residue in vitro. Taken together, the data suggest that MMP-7 directly mediates shedding of syndecan-2 from colon cancer cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Colonic Neoplasms / metabolism*
  • Humans
  • Matrix Metalloproteinase 7 / genetics
  • Matrix Metalloproteinase 7 / metabolism*
  • Protein Structure, Tertiary
  • Syndecan-2 / metabolism*
  • Transcription Factors
  • Tripartite Motif Proteins
  • Ubiquitin-Protein Ligases

Substances

  • Transcription Factors
  • Tripartite Motif Proteins
  • Syndecan-2
  • TRIM32 protein, human
  • Ubiquitin-Protein Ligases
  • MMP7 protein, human
  • Matrix Metalloproteinase 7