KiSS‑1‑mediated suppression of the invasive ability of human pancreatic carcinoma cells is not dependent on the level of KiSS‑1 receptor GPR54.
KiSS‑1‑mediated suppression of the invasive ability of human pancreatic carcinoma cells is not dependent on the level of KiSS‑1 receptor GPR54.
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KiSS-1介导的对人胰腺癌细胞侵袭能力的抑制不依赖于KiSS-1受体GPR54的水平
DOI：
10.3892/mmr.2015.4535
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发表时间：
2016-01
影响因子：
3.4
通讯作者：
Zhou WP
中科院分区：
文献类型：
--
作者：
Wang CH;Qiao C;Wang RC;Zhou WP
胰腺癌局部浸润和淋巴转移的发生限制了手术干预和其他治疗后的生存率。KiSS-1在胰腺癌中的表达降低与癌症转移有关。已有研究表明KiSS-1肽Kisspeptin能够与其受体GPR 54（hOT 7 T175）结合并抑制PANC-1胰腺癌细胞的迁移。KiSS-1的转移抑制是否依赖于胰腺癌细胞系中GPR 54的水平仍不清楚。人BxPC-3胰腺癌细胞高度分化而不表现出转移，然而PANC-1胰腺癌细胞分化差并且表现出局部和淋巴结转移。与原代培养的滋养层细胞相比，观察到BxPc-3和PANC-1细胞表达低水平的KiSS-1 mRNA和蛋白，分别使用逆转录-定量聚合酶链反应和蛋白质印迹法测量。然而，与BxPc-3细胞相比，在PANC-1细胞中观察到更高的GPR 54 mRNA和蛋白表达水平。MTT法检测KiSS-1对BxPc-3和PANC-1细胞增殖的影响。转染KiSS-1后BxPc-3和PANC-1细胞的增殖与对照组相比无显著性差异（P>0.05）。Matrigel包被的Transwell法检测BxPc-3和PANC-1细胞的体外侵袭能力，KiSS-1过表达48 h后，BxPc-3和PANC-1细胞的侵袭指数明显降低（P<0.05）。转染KiSS-1后48 h，BxPc-3和PANC-1细胞中KiSS-1 mRNA和蛋白表达水平显著升高（P<0.05），而GPR 54表达水平无明显变化（P>0.05）。KiSS-1是胰腺癌的转移抑制基因，并且这种抑制不依赖于GPR 54的表达水平。因此，KiSS-1可能成为基因治疗的新靶点。
The onset of local invasion and lymphatic metastasis in pancreatic cancer limits survival following surgical intervention and additional therapies. Reduced expression of KiSS-1 in pancreatic cancer is associated with cancer metastasis. Previous studies have indicated that kisspeptin, the KiSS-1 peptide, is able to bind to its receptor-GPR54 (hOT7T175) and suppress the migration of PANC-1 pancreatic cancer cells. Whether the metastatic suppression of KiSS-1 is dependent on the levels of GPR54 in pancreatic cancer cell lines remains unclear. Human BxPC-3 pancreatic carcinoma cells are highly differentiated without exhibiting metastasis, however PANC-1 pancreatic carcinoma cells are poorly differentiated and exhibit local and lymph node metastasis. Compared with primary cultured trophoblasts, BxPc-3 and PANC-1 cells were observed to express low levels of KiSS-1 mRNA and protein, measured using reverse transcription-quantitative polymerase chain reaction and western blotting, respectively. However, greater mRNA and protein expression levels of GPR54 were observed in PANC-1 cells compared with BxPc-3 cells. An MTT assay was used to investigate the effect of KiSS-1 on BxPc-3 and PANC-1 cell proliferation. There were no significant differences in proliferation following transfection with KiSS-1 in BxPc-3 and PANC-1 cells compared with the controls (P>0.05). A Transwell assay with chambers coated with Matrigel was used to evaluate the in vitro invasive ability of BxPc-3 and PANC-1 cells, with the invasion index of BxPc-3 and PANC-1 cells significantly reduced following 48 h of KiSS-1 overexpression (P<0.05). The mRNA and protein expression levels of KiSS-1 were significantly increased in BxPc-3 and PANC-1 cells 48 h subsequent to transfection with KiSS-1 (P<0.05), while GPR54 expression was not altered (P>0.05). KiSS-1 is a metastasis suppressor gene of pancreatic cancer, and this suppression is not dependent on the expression levels of GPR54. Therefore, KiSS-1 is potentially a novel target for gene therapy.