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

Mi Jung Kwon, Eunkyoung Hong, Youngsil Choi, Duk Hee Kang, Eok Soo Oh

Research output: Contribution to journalArticlepeer-review

33 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)487-492
Number of pages6
JournalBiochemical and Biophysical Research Communications
Volume446
Issue number2
DOIs
StatePublished - 4 Apr 2014

Bibliographical note

Funding Information:
This research was supported by the National Research Foundation of Korea (NRF) Grant funded by the Korea Government (MEST) (No. 2012R1A5A1048236, 2013R1A2A2A01013565) and Korean Health Technology R&D Project, Ministry of Health & Welfare, Republic of Korea. (HI12C0050).

Keywords

  • Extracellular matrix
  • Interleukin
  • Matrix metalloproteinase
  • Syndecan

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