KLK6 Promotes Growth, Migration, and Invasion of Gastric Cancer Cells

Shengxing Zhu; Jihua Shi; Shanfeng Zhang; Zhen Li

doi:10.5230/jgc.2018.18.e35

KLK6 Promotes Growth, Migration, and Invasion of Gastric Cancer Cells

J Gastric Cancer. 2018 Dec;18(4):356-367. doi: 10.5230/jgc.2018.18.e35. Epub 2018 Nov 14.

Authors

Shengxing Zhu^{1

2}, Jihua Shi¹, Shanfeng Zhang³, Zhen Li⁴

Affiliations

¹ Department of Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
² Department of The Second General Surgery, People's Hospital of Zhengzhou, Zhengzhou, China.
³ School of Basic Medicine, Zhengzhou University, Zhengzhou, China.
⁴ Department of Gastrointestinal Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.

Abstract

Purpose: Kallikrein (KLK) proteases are hormone-like signaling molecules with critical functions in different cancers. This study investigated the expression of KLK6 in gastric cancer and its potential role in the growth, migration, and invasion of gastric cancer cells.

Materials and methods: In this study, we compared protein levels of KLK6, vascular endothelial growth factor (VEGF), and matrix metallopeptidase (MMP) 9 in normal gastric epithelial and gastric cancer cell lines by western blot. Fluorescence-activated cell sorting was employed to sort 2 clones of SGC-7901 cells with distinct KLK6 expression, namely, KLK6-high (KLK6^high) and KLK6-low (KLK6^low), which were then expanded. Lastly, immunohistochemical analysis was performed to investigate KLK6 expression in gastric cancer patients.

Results: The expression levels of KLK6, VEGF, and MMP 9, were significantly higher in the gastric cancer cell lines SGC-7901, BGC-823, MKN-28, and MGC-803 than in the normal gastric epithelial cell line GES-1. Compared to KLK6^low cells, KLK6^high cells showed enhanced viability, colony-forming ability, migration, and invasion potential in vitro. Importantly, immunohistochemical analysis of a human gastric cancer tissue cohort revealed that the staining for KLK6, VEGF, and MMP9 was markedly stronger in the cancerous tissues than in the adjacent normal tissues. KLK6 expression also correlated with that of VEGF and MMP9 expression, as well as several key clinicopathological parameters.

Conclusions: Together, these results suggest an important role for KLK6 in human gastric cancer progression.

Keywords: Gastric cancer; KLK6 protein, human; MMP9 protein, human; VEGF.