Macrophage inhibitory cytokine-1 induces the invasiveness of gastric cancer cells by up-regulating the urokinase-type plasminogen activator system

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dc.contributor.authorDong Hoon Lee-
dc.contributor.authorYoung Yang-
dc.contributor.authorS J Lee-
dc.contributor.authorKun Yong Kim-
dc.contributor.authorTae Hyeon Kim-
dc.contributor.authorSun Mi Shin-
dc.contributor.authorK S Song-
dc.contributor.authorY H Lee-
dc.contributor.authorY J Kim-
dc.contributor.authorJung Joon Lee-
dc.contributor.authorIn Pyo Choi-
dc.contributor.authorJeong-Hyung Lee-
dc.description.abstractIn our search for genes associated with gastric cancer progression, we identified macrophage inhibitory cytokine-1 (MIC-1), a member of the transforming growth factor β superfamily, as an overexpressed gene in gastric tumor tissues. Expression analysis of MIC-1 in gastric tumor tissues revealed a specific expression in gastric cancer cells, and this expression level was well correlated with invasive potential in various human gastric cancer cell lines. Stable transfection of MIC-1 into SNU-216, a human gastric cancer cell line, significantly increased its invasiveness. The overexpression of MIC-1 into SNU-216 cells significantly increased the activity of urokinase-type plasminogen activator (uPA), and the expressions of uPA and urokinase-type plasminogen activator receptor (uPAR). Similarly, the stimulation of gastric cancer cell lines with purified recombinant MIC-1 dose-dependently increased cell invasiveness, uPA activity, and uPA and uPAR expression. However, MIC-1 did not significantly suppress the proliferation of gastric cancer cell lines. We also found that the stimulation of human gastric cell lines with recombinant MIC-1 strongly induced activation of mitogen-activated protein kinase kinase-1/2 and extracellular signal-regulated kinase-1/2. Additional analysis revealed that PD98059, a selective inhibitor of mitogen-activated protein kinase kinase-1/2, suppressed not only gastric cancer cell invasiveness and uPA activity, but also the mRNA expressions of uPA and uPAR, as induced by recombinant MIC-1. Our results indicate that MIC-1 may contribute to the malignant progression of gastric cancer cells by inducing tumor cell invasion through the up-regulation of the uPA activation system via extracellular signal-regulated kinase-1/2-dependent pathway.-
dc.publisherAmer Assoc Cancer Research-
dc.titleMacrophage inhibitory cytokine-1 induces the invasiveness of gastric cancer cells by up-regulating the urokinase-type plasminogen activator system-
dc.title.alternativeMacrophage inhibitory cytokine-1 induces the invasiveness of gastric cancer cells by up-regulating the urokinase-type plasminogen activator system-
dc.citation.titleCancer Research-
dc.contributor.affiliatedAuthorDong Hoon Lee-
dc.contributor.affiliatedAuthorYoung Yang-
dc.contributor.affiliatedAuthorKun Yong Kim-
dc.contributor.affiliatedAuthorTae Hyeon Kim-
dc.contributor.affiliatedAuthorSun Mi Shin-
dc.contributor.affiliatedAuthorJung Joon Lee-
dc.contributor.affiliatedAuthorIn Pyo Choi-
dc.contributor.affiliatedAuthorJeong-Hyung Lee-
dc.identifier.bibliographicCitationCancer Research, vol. 63, no. 15, pp. 4648-4655-
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Division of Biomedical Research > Immunotherapy Research Center > 1. Journal Articles
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