Protease-Activated Receptor-2 Is Associated With Adverse Outcomes in Canine Mammary Carcinoma

Abstract

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.

Characterization and modulation of the pro‐inflammatory effects of immune cells in the canine intervertebral disk

“…Statistics = linear mixed model with Benjamini-Hochberg.in the human in vitro model with sex differences observed between male and female samples 18. In the canine model, Kaji et al and Kim et al identified a role for PAR2 in canine mammary carcinoma and atopic dermatitis, respectively 44,45. However, outside of the present study, little research has explored PAR2 effects on the inflammatory response of canine IVD cells.…”

“… 18 In the canine model, Kaji et al and Kim et al identified a role for PAR2 in canine mammary carcinoma and atopic dermatitis, respectively. 44 , 45 However, outside of the present study, little research has explored PAR2 effects on the inflammatory response of canine IVD cells. An inability to account for sex differences due to our sample size or dose of PAR2A chosen may explain why we did not see an effect of PAR2A on the canine immune modulatory pathway.…”