title: Interleukin-1α promotes extracellular shedding of syndecan-2 via induction of matrix metalloproteinase-7 expression.
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.
authors.affiliation: Department of Life Sciences, Division of Molecular Life Sciences and Center for Cell Signaling Research, Ewha Womans University, Seoul 120-725, Republic of Korea.
authors.forename: Mi-Jung
authors.initials: MJ
authors.lastname: Kwon
authors.affiliation: Department of Life Sciences, Division of Molecular Life Sciences and Center for Cell Signaling Research, Ewha Womans University, Seoul 120-725, Republic of Korea.
authors.forename: Eunkyoung
authors.initials: E
authors.lastname: Hong
authors.affiliation: Department of Life Sciences, Division of Molecular Life Sciences and Center for Cell Signaling Research, Ewha Womans University, Seoul 120-725, Republic of Korea.
authors.forename: Youngsil
authors.initials: Y
authors.lastname: Choi
authors.affiliation: Division of Nephrology, Department of Internal Medicine, Ewha Womans University School of Medicine, Ewha Medical Research Center, Seoul, Republic of Korea. Electronic address: dhkang@ewha.ac.kr.
authors.forename: Duk-Hee
authors.initials: DH
authors.lastname: Kang
authors.affiliation: Department of Life Sciences, Division of Molecular Life Sciences and Center for Cell Signaling Research, Ewha Womans University, Seoul 120-725, Republic of Korea. Electronic address: OhES@ewha.ac.kr.
authors.forename: Eok-Soo
authors.initials: ES
authors.lastname: Oh
mesh_terms: D003110:Colonic Neoplasms / Q000378:metabolism*; D045325:HCT116 Cells; D019073:HT29 Cells; D006801:Humans; D053582:Interleukin-1alpha / Q000378:metabolism*; D020783:Matrix Metalloproteinase 7 / Q000378:metabolism*; D053669:Syndecan-2 / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: D053582:Interleukin-1alpha; C508245:SDC2 protein, human; D053669:Syndecan-2; C060932:MMP7 protein, human; D020783:Matrix Metalloproteinase 7
keywords: Extracellular matrix; Interleukin; Matrix metalloproteinase; Syndecan