ADAM17 pathway promotes canine mammary tumor cell migration

Abstract Background ADAM17, also known as tumor necrosis factor-converting enzyme (TACE), is a pleiotropic protease that contributes to inflammation and cancer progression by activating epidermal growth factor receptor (EGFR) signaling and IL-6 trans-signaling, among other pathways. Because ADAM17 signaling remains poorly characterized in veterinary pathophysiology, we investigated its biological roles in canine mammary tumors (CMTs), one of the most common cancers in dogs, where treatment options remain limited. Methods ADAM17 mRNA levels were compared between canine mammary carcinoma tissues and normal mammary glands. We also investigated the effects of pharmacological stimulation and/or inhibition of the ADAM17 pathway on key cancer-related biological processes in the FR37-CMT and the FR10-CMT cell lines. Specifically, we assessed cell viability and apoptosis under basal conditions and following doxorubicin treatment. In addition, we examined the impact of ADAM17 pathway modulation on epithelial-to-mesenchymal transition (EMT) and cell motility. Results ADAM17 mRNA expression was significantly upregulated in canine mammary carcinoma tissues with grade II or more compared with normal controls, and its expression may be associated with tumor progression and dissemination. ADAM17 did not appear to play a major role in FR37-CMT cell viability, apoptosis, doxorubicin-mediated cytotoxicity, or EMT. However, ADAM17 was found to promote FR37-CMT and FR10-CMT cell motility. Conclusions These findings suggest that pharmacological inhibition of ADAM17 activity may represent a promising strategy to limit the metastatic spread of mammary cancer in dogs.