College of Medicine and Veterinary Medicine, University of Edinburgh, Royal (Dick) School of Veterinary Studies, University of Edinburgh, United Kingdom.
College of Medicine and Veterinary Medicine, University of Edinburgh, Royal (Dick) School of Veterinary Studies, University of Edinburgh, United Kingdom.
Vet Immunol Immunopathol. 2024 Nov;277:110838. doi: 10.1016/j.vetimm.2024.110838. Epub 2024 Oct 1.
Equine sarcoids are common non-metastasising skin tumours in horses, associated with bovine papillomavirus (BPV) infection. Six subtypes are recognised (occult, verrucose, nodular, fibroblastic, mixed and malevolent lesions), with variable clinical behaviour. The pathophysiology underlying varying tumour phenotype is poorly understood, and previous data on associations with viral load have been conflicting. To better understand this clinical variation, we investigated associations between tumour subtype and viral load, viral early protein gene expression, and expression of 10 host genes by quantitative polymerase chain reaction in 27 sarcoids and 5 normal skin samples. Viral DNA copy number did not differ between subtypes but was significantly higher in animals with fewer tumours. Expression of BPV E2 and E6 was higher in occult lesions compared to fibroblastic or nodular lesions, while E5 expression was higher in previously-treated lesions. Of the host genes, only IL6 and IL1B differed between subtypes, with higher expression in fibroblastic lesions, while IL10 and CCL5 were elevated compared to skin in all lesion types, and elevations in TNF and TGFB1 were significant for occult lesions only. Expression of TLR9, ATR, VEGFA and PTGS2 in sarcoids was not significantly different from normal skin, suggesting differences between BPV and human papillomavirus tumorigenesis. Results for BPV viral load and gene expression differed from previous reports and are insufficient to explain the spectrum of tumour phenotypes. Activation of both pro-inflammatory and anti-inflammatory immune pathways in sarcoids could influence tumour growth and effective immune responses, and the contribution of specific infiltrating immune cells requires further investigation.
马的肉瘤是一种常见的非转移性皮肤肿瘤，与牛乳头瘤病毒（BPV）感染有关。现已识别出 6 种亚型（隐匿型、疣状型、结节型、成纤维细胞型、混合性和恶性病变），其临床行为具有变异性。肿瘤表型差异的病理生理学机制尚不清楚，之前关于与病毒载量关联的数据存在冲突。为了更好地理解这种临床变异，我们通过定量聚合酶链反应（qPCR），在 27 个肉瘤和 5 个正常皮肤样本中，研究了肿瘤亚型与病毒载量、病毒早期蛋白基因表达和 10 个宿主基因表达之间的关联。不同亚型之间的病毒 DNA 拷贝数没有差异，但在肿瘤较少的动物中，病毒载量显著较高。与成纤维细胞瘤或结节性病变相比，隐匿性病变中 BPV E2 和 E6 的表达较高，而 E5 的表达在先前治疗过的病变中较高。在宿主基因中，只有 IL6 和 IL1B 在不同亚型之间存在差异，成纤维细胞瘤中表达较高，而所有病变类型中 IL10 和 CCL5 均高于皮肤，仅隐匿性病变中 TNF 和 TGFB1 的升高具有显著性。肉瘤中 TLR9、ATR、VEGFA 和 PTGS2 的表达与正常皮肤无显著差异，这表明 BPV 和人乳头瘤病毒的肿瘤发生机制存在差异。BPV 病毒载量和基因表达的结果与之前的报告不同，不足以解释肿瘤表型的范围。肉瘤中促炎和抗炎免疫途径的激活都可能影响肿瘤的生长和有效的免疫反应，特定浸润免疫细胞的贡献需要进一步研究。
