Zhu Shengxing, Shi Jihua, Zhang Shanfeng, Li Zhen
Department of Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
Department of The Second General Surgery, People's Hospital of Zhengzhou, Zhengzhou, China.
J Gastric Cancer. 2018 Dec;18(4):356-367. doi: 10.5230/jgc.2018.18.e35. Epub 2018 Nov 14.
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.
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) and KLK6-low (KLK6), which were then expanded. Lastly, immunohistochemical analysis was performed to investigate KLK6 expression in gastric cancer patients.
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 cells, KLK6 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.
Together, these results suggest an important role for KLK6 in human gastric cancer progression.
激肽释放酶（KLK）蛋白酶是一类激素样信号分子，在不同癌症中发挥关键作用。本研究旨在调查KLK6在胃癌中的表达及其在胃癌细胞生长、迁移和侵袭中的潜在作用。
在本研究中，我们通过蛋白质印迹法比较了正常胃上皮细胞系和胃癌细胞系中KLK6、血管内皮生长因子（VEGF）和基质金属蛋白酶（MMP）9的蛋白水平。采用荧光激活细胞分选技术对SGC-7901细胞中KLK6表达不同的两个克隆进行分选，即KLK6高表达（KLK6）和KLK6低表达（KLK6），然后进行扩增。最后，通过免疫组织化学分析研究KLK6在胃癌患者中的表达情况。
胃癌细胞系SGC-7901、BGC-823、MKN-28和MGC-803中KLK6、VEGF和MMP 9的表达水平显著高于正常胃上皮细胞系GES-1。与KLK6细胞相比，KLK6细胞在体外表现出更强的活力、集落形成能力、迁移和侵袭潜力。重要的是，对一组人胃癌组织的免疫组织化学分析显示，癌组织中KLK6、VEGF和MMP9的染色明显强于相邻正常组织。KLK6表达还与VEGF和MMP9表达以及几个关键临床病理参数相关。
这些结果共同表明KLK6在人类胃癌进展中起重要作用。
