Qilu Hospital of Shandong University, Jinan 250012, Shandong Province, China.
Department of Critical Care Medicine, Shandong Traffic Hospital, Jinan 250000, Shandong Province, China.
World J Gastroenterol. 2018 Mar 14;24(10):1120-1133. doi: 10.3748/wjg.v24.i10.1120.
To clarify the role of proteinase-activated receptor 2 (PAR2) in hepatocellular carcinoma, especially in the process of metastasis.
PAR2 expression levels were assessed by qRT-PCR and immunohistochemistry (IHC) in patient tissues and in hepatocellular carcinoma cell lines SMMC-7721 and HepG2. Cell proliferation and metastasis were assessed both and . Immunoblotting was carried out to monitor the levels of mitogen-activated protein kinase (MAPK) and epithelial-mesenchymal transition markers.
The prognosis was significantly poorer in patients with high PAR2 levels than in those with low PAR2 levels. Patients with high PAR2 levels had advanced tumor stage ( = 0.001, chi-square test), larger tumor size ( = 0.032, chi-square test), and high microvascular invasion rate ( = 0.037, chi-square test). The proliferation and metastasis ability of SMMC-7721 and HepG2 cells was increased after PAR2 overexpression, while knockdown of PAR2 decreased the proliferation and metastasis ability of SMMC-7721 and HepG2 cells. Knockdown of PAR2 also inhibited hepatocellular carcinoma tumor cell growth and liver metastasis in nude mice. Mechanistically, PAR2 increased the proliferation ability of SMMC-7721 and HepG2 cells ERK activation. Activated ERK further promoted the epithelial-mesenchymal transition of these cells, which endowed them with enhanced migration and invasion ability.
These data suggest that PAR2 plays an important role in the proliferation and metastasis of hepatocellular carcinoma. Therefore, targeting PAR2 may present a favorable target for treatment of this malignancy.
阐明蛋白酶激活受体 2（PAR2）在肝细胞癌中的作用，特别是在转移过程中的作用。
通过 qRT-PCR 和免疫组织化学（IHC）评估患者组织和肝细胞癌细胞系 SMMC-7721 和 HepG2 中 PAR2 的表达水平。通过[细胞]和[动物]实验评估细胞增殖和转移。免疫印迹用于监测丝裂原活化蛋白激酶（MAPK）和上皮-间充质转化标志物的水平。
PAR2 水平高的患者预后明显差于 PAR2 水平低的患者。PAR2 水平高的患者肿瘤分期较晚（=0.001，卡方检验），肿瘤较大（=0.032，卡方检验），微血管侵犯率较高（=0.037，卡方检验）。过表达 PAR2 后，SMMC-7721 和 HepG2 细胞的增殖和转移能力增加，而 PAR2 敲低则降低了 SMMC-7721 和 HepG2 细胞的增殖和转移能力。PAR2 敲低还抑制了裸鼠肝癌肿瘤细胞的生长和肝转移。机制上，PAR2 通过激活 ERK 增加了 SMMC-7721 和 HepG2 细胞的增殖能力。激活的 ERK 进一步促进了这些细胞的上皮-间充质转化，赋予它们增强的迁移和侵袭能力。
这些数据表明 PAR2 在肝细胞癌的增殖和转移中发挥重要作用。因此，靶向 PAR2 可能为治疗这种恶性肿瘤提供一个有利的靶点。
