Lysophosphatidic acid signaling via LPA1 and LPA3 regulates cellular functions during tumor progression in pancreatic cancer cells
Lysophosphatidic acid signaling via LPA1 and LPA3 regulates cellular functions during tumor progression in pancreatic cancer cells
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DOI：
10.1016/j.yexcr.2017.02.007
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发表时间：
2017-03-01
影响因子：
3.7
通讯作者：
Tsujiuchi, Toshifumi
中科院分区：
文献类型：
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作者：
Fukushima, Kaori;Takahashi, Kaede;Tsujiuchi, Toshifumi
溶血磷脂酸（LPA）信号通过G蛋白偶联的LPA受体表现出多种生物学效应，如细胞增殖、运动和分化。本研究的目的是评估LPA（1）和LPA（3）在胰腺癌细胞肿瘤进展过程中的细胞功能中的作用。从PANC-1细胞产生LPA（1）和LPA（3）敲低细胞。LPA（1）和LPA（3）基因敲低可抑制PANC-1细胞的运动和侵袭能力。在明胶酶谱中，LPA（1）和LPA（3）敲低的细胞表明在LPA存在下基质金属蛋白酶-2（MMP-2）的低活化。接下来，为了评估LPA 1和LPA 3是否调节由抗癌药物诱导的细胞功能，用顺铂（CDDP）处理PANC-1细胞约6个月。CDDP长期处理的PANC-1细胞的运动和侵袭能力明显高于对照组，且与LPAR 1和LPAR 3基因表达水平相关。在软琼脂试验中，长期CDDP处理的细胞形成明显大尺寸的集落。此外，LPA（1）和LPA（3）的敲低以及集落形成显著抑制了CDDP增强的细胞运动和侵袭活性。这些结果表明，通过LPA（1）和LPA（3）的LPA信号传导在PANC-1细胞中肿瘤进展期间的细胞功能调节中起重要作用。
Lysophosphatidic acid (LPA) signaling via G protein -coupled LPA receptors exhibits a variety of biological effects, such as cell proliferation, motility and differentiation. The aim of this study was to evaluate the roles of LPA(1) and LPA(3) in cellular functions during tumor progression in pancreatic cancer cells. LPA(1) and LPA(3) knockdown cells were generated from PANC-1 cells. The cell motile and invasive activities of PANC-1 cells were inhibited by LPA(1) and LPA(3) knockdown. In gelatin zymography, LPA(1) and LPA(3) knockdown cells indicated the low activation of matrix metalloproteinase-2 (MMP-2) in the presence of LPA. Next, to assess whether LPA1 and LPA3 regulate cellular functions induced by anticancer drug, PANC-1 cells were treated with cisplatin (CDDP) for approximately 6 months. The cell motile and invasive activities of long-term CDDP treated cells were markedly higher than those of PANC-1 cells, correlating with the expression levels of LPARI and LPAR3 genes. In soft agar assay, the long-term CDDP treated cells formed markedly large sized colonies. In addition, the cell motile and invasive activities enhanced by CDDP were significantly suppressed by LPA(1) and LPA(3) knockdown as well as colony formation. These results suggest that LPA signaling via LPA(1) and LPA(3) play an important role in the regulation of cellular functions during tumor progression in PANC-1 cells.