Procópio de Oliveira Caroline, Frigieri Barbara Maria, Fukumasu Heidge, Chuffa Luiz Gustavo de Almeida, Novais Adriana Alonso, Zuccari Debora Aparecida Pires de Campos
Cancer Molecular Research Laboratory (LIMC), Faculdade de Medicina de São José do Rio Preto-FAMERP, Av. Brigadeiro Faria Lima, São José do Rio Preto 15090-000, SP, Brazil.
Postgraduate Program in Health Sciences, Faculdade de Medicina de São José do Rio Preto-FAMERP, Av. Brigadeiro Faria Lima, 5416, São José do Rio Preto 15090-000, SP, Brazil.
Biomedicines. 2023 Oct 19;11(10):2837. doi: 10.3390/biomedicines11102837.
(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.
(1) 背景：雌性犬的乳腺肿瘤与人类相同类型的肿瘤有许多相似之处，使这些动物成为研究乳腺癌新疗法的宝贵临床前模型。细胞外囊泡（EVs），特别是外泌体，通过将特定蛋白质转移到肿瘤微环境中的受体细胞，在乳腺癌发生过程中发挥着复杂的作用，凸显了它们的重要性。褪黑素，一种以其抗肿瘤作用而闻名的激素，又增添了一层神秘色彩。(2) 方法：从诊断患有乳腺肿瘤的犬的血浆中获得的细胞外囊泡与良性上皮谱系E - 20使用DMEM共同培养。该实验包括四个24小时治疗组：对照组、细胞外囊泡组、褪黑素组和细胞外囊泡 + 褪黑素组。进行了一系列测定，包括集落形成、增殖和细胞迁移评估。此外，我们还进行了集落形成、增殖和细胞迁移测定。我们对mTOR途径的蛋白质，包括mTOR和AKT进行了免疫组织化学检测。(3) 结果：单独的外泌体显著提高了增殖、迁移和集落形成率，并上调了mTOR和AKT蛋白的表达。然而，当添加褪黑素时，观察到了保护作用。(4) 结论：这些发现有助于在乳腺肿瘤的临床兽医肿瘤学中使用褪黑素调节细胞外囊泡介导的信号传导。
