Protease-Activated Receptor-2 Is Associated With Adverse Outcomes in Canine Mammary Carcinoma
Protease-Activated Receptor-2 Is Associated With Adverse Outcomes in Canine Mammary Carcinoma
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DOI：
10.1177/0300985820963087
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发表时间：
2021-01-01
影响因子：
2.4
通讯作者：
Maeda, Shingo
中科院分区：
文献类型：
--
作者：
Kaji, Kenjiro;Kaji, Noriyuki;Maeda, Shingo
蛋白酶激活受体2（PAR 2）是一种G蛋白偶联受体，可被丝氨酸蛋白酶激活。在人类中，PAR 2在包括乳腺癌在内的各种癌症中高度表达，并且与癌症进展和转移相关。然而，PAR 2在犬乳腺癌中的表达和作用尚不清楚。本研究的目的是检测PAR 2在犬乳腺癌中的表达，PAR 2表达与临床特征之间的关系，以及PAR 2在肿瘤细胞转移表型中的作用。采用免疫组织化学方法检测31例犬乳腺癌组织和10例正常乳腺组织中PAR 2的表达。正常乳腺不表达PAR 2。与此相反，乳腺癌显示PAR 2免疫反应性的细胞质中，其表达水平从阴性到强阳性标本之间的变化。PAR 2高表达的犬的总体生存期短于PAR 2低表达的犬。此外，PAR 2表达水平与淋巴结转移、晚期临床分期和高组织病理学分级相关。体外分析表明，PAR 2激动剂加速了犬乳腺癌细胞系中的细胞迁移和侵袭。此外，PAR 2激动剂诱导上皮-间充质转化和肌动蛋白聚合。这些结果表明PAR 2表达在犬乳腺癌的肿瘤进展和临床结果中起作用。
Protease-activated receptor-2 (PAR2) is a G protein-coupled receptor that is activated by serine proteases. In humans, PAR2 is highly expressed in various cancers, including breast cancer, and is associated with cancer progression and metastasis. However, the expression and roles of PAR2 in canine mammary carcinoma remain unclear. The purpose of this study was to examine the expression of PAR2 in canine mammary carcinoma, the association between PAR2 expression and clinical characteristics, and the role of PAR2 in the metastatic phenotypes of tumor cells. Mammary carcinoma from 31 dogs and 10 normal mammary glands were included in this study, and used for immunohistochemical analysis of PAR2 expression. Normal mammary glands did not express PAR2. In contrast, mammary carcinomas showed PAR2 immunoreactivity in the cytoplasm, and its expression level varied between specimens from negative to strongly positive. The overall survival of dogs with high PAR2 expression was shorter than that of dogs with low PAR2 expression. Moreover, PAR2 expression level was associated with the presence of lymph node involvement, advanced clinical stage, and high histopathological grade. In vitro analyses revealed that a PAR2 agonist accelerated cell migration and invasion in a canine mammary carcinoma cell line. In addition, the PAR2 agonist induced epithelial-mesenchymal transition and actin polymerization. These results suggest that PAR2 expression plays a role in tumor progression and clinical outcomes in canine mammary carcinoma.