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

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

Affiliations
  • 1Department of Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China. shengxing_zhu@sina.com
  • 2Department of The Second General Surgery, People's Hospital of Zhengzhou, Zhengzhou, China.
  • 3School of Basic Medicine, Zhengzhou University, Zhengzhou, China.
  • 4Department 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 (KLK6high) and KLK6-low (KLK6low), 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 KLK6low cells, KLK6high 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.

Keyword

Gastric cancer; KLK6 protein, human; MMP9 protein, human; VEGF

MeSH Terms

Blotting, Western
Cell Line
Clone Cells
Cohort Studies
Epithelial Cells
Flow Cytometry
Humans
In Vitro Techniques
Kallikreins
Peptide Hydrolases
Stomach Neoplasms*
Vascular Endothelial Growth Factor A
Kallikreins
Peptide Hydrolases
Vascular Endothelial Growth Factor A
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