HGF Mediated Upreulation of Lipocalin 2 Regulates MMP9 through Nuclear Factor-kB Activation in Gastric Cancer - ICMS2015 Abstract Submission Form Tumor Microenvironment Conference

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¹Departments of Hematology-Oncology, College of Medicine, Yeungnam University, South Korea
²Departments of Surgery, College of Medicine, Yeungnam University, South Korea
³Departments of Biochemistry and Molecular Biology, Aging Associated Vascular Disease Research Center, College of Medicine, Yeungnam University, South Korea
⁴Departments of GastroEnterology, College of Medicine, Yeungnam University, South Korea
⁵Departments of Hematology-Oncology, VHS Medical Center, South Korea

Lipocalin 2(LCN2) is a member of lipocalin family that binds and transports small lipophilic ligand, sharing a highly conserved tertiary structure and can be found as a monomer, homodimer, heterodimer with MMP9. Some reported that high molecule of LCN2/MMP9 complex was founded in several types. But, the mechanisms of regulation between LCN2 with MMP9 in tumorigenesis. . The aims of this study were to identify of function of LCN2 associated with MMP9 in gastric cancer growth and metastasis.

First, we confirmed that the expression level of LCN2 and MMP9 was upregulated by HGF(hepatocyte growth factor). To identify association pathway of HGF-induced LCN2, the cells were treated with PI3-kinase inhibitor(LY294002) or MEK inhibitor(PD098059) or p38 inhibitor(SB203580) and then analyzed by Western blotting. The HGF-mediated LCN2 protein level was only decreased with LY294002. Also, the HGF-mediated MMP9 was decreased with LY294002. The role for LCN2 with HGF mediated MMP9 was determined by knock down cell of LCN2. LCN2-sh RNA cells showed a decreased level of HGF-mediated MMP9. The HGF-mediated LCN2 protein level was decreased with treatment of NFkB inhibitor. We confirmed the role of HGF-mediated LCN2. HGF-mediated cell proliferation and in vitro invasion was decreased in LCN2 knock down cell.

In conclusion, our study showed that LCN2 upregulated MMP9 through PI3K/AKT/NFkB pathway in gastric cancer. And LCN2 have a role in cell proliferation and cell invasion in gastric cancer, which may be a possible target for developing gastric cancer therapy.