Different roles of GPR120 and GPR40 in the acquisition of malignant properties in pancreatic cancer cells
Different roles of GPR120 and GPR40 in the acquisition of malignant properties in pancreatic cancer cells
复制标题
DOI：
10.1016/j.bbrc.2015.08.050
复制
发表时间：
2015-09-25
影响因子：
3.1
通讯作者：
Tsujiuchi, Toshifumi
中科院分区：
文献类型：
--
作者：
Fukushima, Kaori;Yamasaki, Eri;Tsujiuchi, Toshifumi
游离脂肪酸（FFA）通过与G蛋白偶联FFA受体（FFARs）结合而发挥细胞外信号分子的作用。GPR 120和GPR 40被鉴定为中链和长链脂肪酸的FFAR。在本研究中，我们研究GPR 120和GPR 40在胰腺癌PANC-1细胞的细胞功能中的作用，使用GPR 120和GPR 40敲低细胞（分别为PANC-sh 120和PANC-sh 40细胞）。在细胞运动实验中，PANC-sh 120细胞的运动能力明显低于对照细胞。相反，PANC-sh 40细胞的细胞运动性显著高于对照细胞。明胶酶谱法测定基质金属蛋白酶（MMPs）的活性水平。PANC-sh 120细胞MMP-2活性降低，而PANC-sh 40细胞MMP-2活性显著高于对照组。另一方面，在所有细胞中均未检测到MMP-9的活化。集落形成实验中，PANC-sh 40细胞形成了大量集落。在PANC-sh 120细胞和对照细胞中未观察到集落形成。这些结果表明，GPR 120和GPR 40的不同作用涉及胰腺癌细胞恶性性质的获得。(C)2015 Elsevier Inc. All rights reserved.
Free fatty acids (FFAs) act as extracellular signaling molecules through binding to G-protein-coupled FFA receptors (FFARs). GPR120 and GPR40 are identified as FFARs for medium- and long-chain fatty acids. In the present study, we investigated roles of GPR120 and GPR40 in cellular functions of pancreatic cancer PANC-1 cells, using GPR120 and GPR40 knockdown cells (PANC-sh120 and PANC-sh40 cells respectively). In cell motility assay, PANC-sh120 cells showed the low cell motility, compared with control cells. In contrast, the cell motility of PANC-sh40 cells was significantly higher than that of control cells. Activity levels of matrix metalloproteinases (MMPs) were measured by gelatin zymography. While PANC-sh120 cells indicated the reduced MMP-2 activity, MMP-2 activity in PANC-sh40 cells was significantly higher than that in control cells. On the other hand, no activation of MMP-9 was detected in all cells. In colony assay, the large sized colonies were markedly formed in PANC-sh40 cells. No colony formation was observed in PANC-sh120 cells as well as control cells. These results suggest that distinct effects of GPR120 and GPR40 are involved in the acquisition of malignant property in pancreatic cancer cells. (C) 2015 Elsevier Inc. All rights reserved.