(1) Background:
Mammary neoplasms in female dogs share many similarities with the same
tumor class in humans, rendering these animals a valuable preclinical model for studying novel
therapies against
breast cancer. The intricate role of extracellular vesicles (EVs), particularly exosomes, in breast
carcinogenesis, by transferring specific
proteins to recipient cells within the tumor microenvironment, underscores their significance.
Melatonin, a
hormone recognized for its antitumor effects, adds another layer of intrigue. (2) Methods: EVs obtained from the plasma of dogs diagnosed with mammary
tumors were co cultivated with the benign epithelial lineage E-20 using DMEM. The experiment comprised four 24 h treatment groups: control, EVs,
melatonin, and EVs +
melatonin. A series of assays were conducted, including colony formation, proliferation, and cellular migration assessments. Furthermore, we conducted colony formation, proliferation, and cellular migration assays. We performed immunohistochemistry for
proteins of the mTOR pathway, including mTOR and AKT. (3) Results: Exosomes alone significantly increased proliferation, migration, and colony formation rates and, upregulated the expression of mTOR and AKT
proteins. However, when
melatonin was added, a protective effect was observed. (4) Conclusions: These findings contributed to the use of
melatonin to modulate EV-mediated signaling in the clinical veterinary oncology of mammary
tumors.