Canine melanoma is a malignant tumour that exhibits aggressive behaviour, and frequently metastasizes to regional lymph nodes and distant sites. Currently, there are no effective treatments or practical prognostic biomarkers for canine melanoma. The enzyme kynurenine 3‐monooxygenase (KMO), which plays a central role in the tryptophan metabolism, has previously been identified as the main pathogenic factor in neurodegenerative diseases; however, it has recently been found to be positively associated with tumour malignancy in human hepatocellular carcinoma and canine mammary tumours. Signal transducer and activator of transcription 3 (STAT3) is a well‐known oncoprotein contributing to the proliferation, survival, invasiveness and metastasis of a variety of cancers. Although whether STAT3 and KMO collaborate in tumorigenesis needs to be further verified, our previous findings showed that inhibition of KMO activity reduced activation of STAT3. This study investigated the expressions of KMO and STAT3/phosphorylated (pSTAT3) by immunohistochemical analysis in 85 cases of canine melanoma, showing their expression levels were high within highly mitotic melanoma cells. KMO Overexpression was significantly associated with increased STAT3 and pSTAT3 expressions. Melanoma tissues with higher KMO, STAT3 and pSTAT3 protein expressions were correlated with reduced survival rates of the canine patients. Moreover, inhibition of KMO activity in canine melanoma cells resulted in reduced cell viability, in addition to decreased expressions of STAT3 and pSTAT3. Our results indicated the significance of KMO and the potential role of KMO/STAT3 interaction in enhancing tumour development. Additionally, KMO and STAT3/pSTAT3 may be viewed as useful biomarkers for the prediction of prognosis of canine melanoma.

中文翻译：

---

犬尿氨酸 3-单加氧酶 (KMO) 和信号转导和转录激活因子 3 (STAT3) 表达参与肿瘤增殖并预测犬黑色素瘤的不良存活率

犬黑色素瘤是一种表现出侵略行为的恶性肿瘤，经常转移到区域淋巴结和远处部位。目前，对于犬黑色素瘤没有有效的治疗方法或实用的预后生物标志物。犬尿氨酸 3-单加氧酶 (KMO) 在色氨酸代谢中起核心作用，此前已被确定为神经退行性疾病的主要致病因素；然而，最近发现它与人肝细胞癌和犬乳腺肿瘤中的肿瘤恶性肿瘤呈正相关。信号转导和转录激活因子 3 (STAT3) 是一种众所周知的癌蛋白，有助于多种癌症的增殖、存活、侵袭和转移。尽管 STAT3 和 KMO 是否在肿瘤发生中协同作用需要进一步验证，但我们之前的研究结果表明，抑制 KMO 活性会降低 STAT3 的激活。本研究通过免疫组织化学分析研究了 85 例犬黑色素瘤中 KMO 和 STAT3/磷酸化 (pSTAT3) 的表达，表明它们在高度有丝分裂的黑色素瘤细胞中的表达水平很高。KMO 过表达与 STAT3 和 pSTAT3 表达增加显着相关。具有较高 KMO、STAT3 和 pSTAT3 蛋白表达的黑色素瘤组织与犬患者的存活率降低相关。此外，犬黑色素瘤细胞中 KMO 活性的抑制导致细胞活力降低，以及 STAT3 和 pSTAT3 的表达降低。我们的结果表明 KMO 的重要性以及 KMO/STAT3 相互作用在促进肿瘤发展中的潜在作用。此外，KMO 和 STAT3/pSTAT3 可被视为预测犬黑色素瘤预后的有用生物标志物。