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28 October 2020 : Laboratory Research  

Upregulation of Serine Proteinase Inhibitor Clade B Member 3 (SERPINB3) Expression by Stromal Cell-Derived Factor (SDF-1)/CXCR4/Nuclear Factor kappa B (NF-κB) Promotes Migration and Invasion of Gastric Cancer Cells

Jing Gong1ABCDEF, Yongxi Song2AB, Ling Xu3ACEF, Xiaofang Che3DEF, Kezuo Hou3BC, Tianshu Guo3BC, Yu Cheng3ABG, Yunpeng Liu3ADE*, Xiujuan Qu3AG

DOI: 10.12659/MSM.927411

Med Sci Monit 2020; 26:e927411

Abstract

BACKGROUND: Serine proteinase inhibitor clade B member 3 (SERPINB3) is a neutral glycoprotein. Its overexpression is related to the promotion of cell proliferation and activation via the nuclear factor kappa B (NF-κB) pathway in several tumors. Whether it can participate in stromal cell-derived factor (SDF-1)/NF-κB-induced metastasis of gastric cancer has not been reported.

MATERIAL AND METHODS: We analyzed the ability of SDF-1 to induce migration and invasion in vitro by knocking down the expression of SERPINB3 with siRNAs in gastric cancer cells. We also explored the effects of a CXCR4 antagonist and NF-κB inhibitor on SERPINB3 expression. We verified the effect of SERPINB3 on prognosis in gastric cancer specimens by immunohistochemistry.

RESULTS: In vitro experiments confirmed that SDF-1 upregulated the expression of SERPINB3 and promoted metastasis in gastric cancer cells. This phenomenon was reversed by knockdown of SERPINB3, a chemokine receptor 4 (CXCR4) antagonist, and an NF-κB inhibitor, which downregulated the expression of SERPINB3. In patients with gastric cancer, a significant positive correlation was observed between CXCR4 and SERPINB3 expression (r=0.222, P=0.029). Moreover, double positivity for SERPINB3 and CXCR4 was certified to be an independent prognostic factor (HR=3.332, P<0.001). CXCR4-positive patients who also expressed SERPINB3 were inclined to suffer from lymph node metastasis, confirming that SERPINB3 is a downstream molecule of CXCR4.

CONCLUSIONS: In vitro and pathological results showed that SDF-1/CXCR4 activated the NF-κB pathway and upregulated SERPINB3 to facilitate the migration and invasion of gastric cancer cells.

Keywords: Chemokine CXCL12, Serpins, Stomach Neoplasms

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Medical Science Monitor eISSN: 1643-3750
Medical Science Monitor eISSN: 1643-3750