Interleukin-1α promotes extracellular shedding of syndecan-2 via induction of matrix metalloproteinase-7 expression

Biochem Biophys Res Commun. 2014 Apr 4;446(2):487-92. doi: 10.1016/j.bbrc.2014.02.142. Epub 2014 Mar 12.


The cell surface heparan sulfate proteoglycan, syndecan-2, is known to play an important role in the tumorigenic activity of colon cancer cells. In addition, the extracellular domain of syndecan-2 is cleaved by matrix metalloproteinase-7 (MMP-7) in various colon cancer cells, but factors involved in regulating this process remain unknown. Here, we demonstrate a role for interleukin-1α (IL-1α) in syndecan-2 shedding in colon cancer cells. Treatment of low metastatic (HT-29) and highly metastatic (HCT-116) colon cancer cells with various soluble growth factors and cytokines revealed that IL-1α specifically increased extracellular shedding of syndecan-2 in a concentration- and time-dependent manner. IL-1α did not affect the expression of syndecan-2, but did significantly reduce its cell surface levels. Notably, IL-1α increased the mRNA expression and subsequent secreted levels of MMP-7 protein and enhanced the phosphorylation of p38 and ERK mitogen-activated protein kinases. Furthermore, increased syndecan-2 shedding was dependent on the mitogen-activated protein kinase-mediated MMP-7 expression. Taken together, these data suggest that IL-1α regulates extracellular domain shedding of syndecan-2 through regulation of the MAP kinase-mediated MMP-7 expression in colon cancer cells.

Keywords: Extracellular matrix; Interleukin; Matrix metalloproteinase; Syndecan.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Colonic Neoplasms / metabolism*
  • HCT116 Cells
  • HT29 Cells
  • Humans
  • Interleukin-1alpha / metabolism*
  • Matrix Metalloproteinase 7 / metabolism*
  • Syndecan-2 / metabolism*
  • Up-Regulation


  • Interleukin-1alpha
  • SDC2 protein, human
  • Syndecan-2
  • MMP7 protein, human
  • Matrix Metalloproteinase 7