School of Biosciences and Veterinary Medicine, University of Camerino, Italy.
Research Institute of Influenza, St-Petersburg, Russia.
Vet Comp Oncol. 2019 Dec;17(4):570-577. doi: 10.1111/vco.12523. Epub 2019 Aug 13.
Recent studies highlighted the role of autophagy as a cardinal regulatory system for homeostasis and cancer-related signalling pathways. In this context, the deregulated expression of p62 - Sequestosome1 (p62/SQSTM1) - a protein acting both as an autophagy receptor and signalling hub, has been associated with tumour development and chronic inflammation. Multiple clinical studies test drugs targeting autophagy, and even more research is on the way to clinical trials. However, no comparative investigations have been carried out to identify adequate preclinical models to assess p62-based medicine. In veterinary oncology the role of p62 in cancer-related pathways has been largely ignored. We compared p62 sequences in multiple organisms and found that canine p62 significantly diverges from the humans and from other animals sequences. Then, we chart by immunohistochemistry the expression levels of p62 in canine mammary tumours. A total of 66 tumours and 10 non-neoplastic mammary samples were examined. The expression of p62 was higher in normal tissue and adenomas than carcinomas, with lowest levels of p62 protein detected in high grade carcinomas. In all cases examined the tumour stroma appeared to be p62-negative. Taken together our results would suggest that in dogs the association between p62 expression and cancer cells overturns that reported in human breast carcinoma, where p62 accumulates in malignant cells as compared to normal epithelium. Thus, at least in canine mammary tumours, p62 should be not considered a tumour-rejection antigen for an anti-cancer immunotherapy.
最近的研究强调了自噬作为维持体内平衡和与癌症相关信号通路的主要调节系统的作用。在这种情况下，p62 - Sequestosome1（p62/SQSTM1）的表达失调 - 一种既作为自噬受体又作为信号枢纽的蛋白质，与肿瘤发展和慢性炎症有关。多项临床研究测试了靶向自噬的药物，更多的研究正在进行临床试验。然而，尚未进行任何比较研究来确定评估基于 p62 的药物的适当临床前模型。在兽医肿瘤学中，p62 在与癌症相关的途径中的作用在很大程度上被忽视了。我们比较了多种生物体中的 p62 序列，发现犬 p62 与人类和其他动物的序列有很大的差异。然后，我们通过免疫组织化学法绘制了犬乳腺肿瘤中 p62 的表达水平。共检查了 66 个肿瘤和 10 个非肿瘤性乳腺样本。p62 在正常组织和腺瘤中的表达高于癌，在高级别癌中检测到最低水平的 p62 蛋白。在所有检查的病例中，肿瘤基质似乎呈 p62 阴性。总之，我们的研究结果表明，在犬中，p62 表达与癌细胞之间的关联与人类乳腺癌中报道的相反，在人类乳腺癌中，p62 积聚在恶性细胞中，而不是正常上皮细胞中。因此，至少在犬乳腺肿瘤中，p62 不应被视为癌症免疫治疗的肿瘤排斥抗原。
