School of Veterinary Medicine, Graduate Institute of Molecular and Comparative Pathobiology, National Taiwan University, Taipei, Taiwan.
Institute of Biotechnology, National Taiwan University, Taipei, Taiwan.
J Cell Mol Med. 2023 Aug;27(15):2183-2193. doi: 10.1111/jcmm.17717. Epub 2023 Jun 19.
Feline injection-site sarcomas (FISSs) are highly invasive malignant mesenchymal neoplasms that arise from injection sites in cats. Although the tumorigenesis of FISSs is still uncertain, there is a consensus that FISS is associated with chronic inflammation caused by irritation of injection-related trauma and foreign chemical substances. Chronic inflammation can provide a proper microenvironment for tumour development, which has been known as one of the risk factors of tumorigenesis in many tumours. To investigate the tumorigenesis of FISS and screen for its potential therapeutic targets, cyclooxygenase-2 (COX-2), an inflammation-enhancing enzyme, was selected as a target for this study. In vitro experiments using FISS- and normal tissue-derived primary cells and robenacoxib, a highly selective COX-2 inhibitor, were performed. The results demonstrated that expression of COX-2 could be detected in formalin-fixed and paraffin-embedded FISS tissues and FISS-derived primary cells. Cell viability, migration and colony formation of FISS-derived primary cells were inhibited, and cell apoptosis was enhanced by robenacoxib in a dose-dependent manner. However, susceptibility to robenacoxib varied in different lines of FISS primary cells and was not completely correlated with COX-2 expression. Our results suggest that COX-2 inhibitors could be potential adjuvant therapeutics against FISSs.
猫注射部位肉瘤（FISSs）是一种高度侵袭性的恶性间叶肿瘤，起源于猫的注射部位。虽然 FISS 的肿瘤发生机制尚不确定，但人们普遍认为 FISS 与注射相关创伤和外来化学物质刺激引起的慢性炎症有关。慢性炎症可以为肿瘤的发展提供适当的微环境，这已被认为是许多肿瘤发生的危险因素之一。为了研究 FISS 的肿瘤发生机制并筛选其潜在的治疗靶点，本研究选择了炎症增强酶环氧化酶-2（COX-2）作为研究目标。进行了 FISS 和正常组织来源的原代细胞以及高度选择性 COX-2 抑制剂罗非昔布的体外实验。结果表明，福尔马林固定和石蜡包埋的 FISS 组织和 FISS 来源的原代细胞中均可检测到 COX-2 的表达。罗非昔布可剂量依赖性地抑制 FISS 来源的原代细胞的细胞活力、迁移和集落形成，并促进细胞凋亡。然而，FISS 原代细胞系对罗非昔布的敏感性不同，且与 COX-2 表达不完全相关。我们的研究结果表明，COX-2 抑制剂可能是 FISSs 的潜在辅助治疗药物。
