Interleukin-1α promotes extracellular shedding of syndecan-2 via induction of matrix metalloproteinase-7 expression.
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| 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.
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| Authors | Mi-Jung Kwon, Eunkyoung Hong, Youngsil Choi, Duk-Hee Kang, Eok-Soo Oh |
| Journal | Biochemical and biophysical research communications (Biochem Biophys Res Commun) Vol. 446 Issue 2 Pg. 487-92 (Apr 04 2014) ISSN: 1090-2104 [Electronic] United States |
| PMID | 24613844 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't) |
| Copyright | Copyright © 2014 Elsevier Inc. All rights reserved. |
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