Retina Service, Ines and Fred Yeatts Retina Research Laboratory, Angiogenesis Laboratory, Department of Ophthalmology, Massachusetts Eye and Ear, Harvard Medical School, Boston, MA, USA.
FEBS Open Bio. 2023 Mar;13(3):545-555. doi: 10.1002/2211-5463.13566. Epub 2023 Feb 12.
Uveal melanoma (UM) is the most common primary intraocular cancer in the adult population. Recent studies suggested that the NLRP3 inflammasome could be a therapeutic target for cutaneous melanoma (CM), but the role of NLRP3 in UM remains unknown. Here, we analyzed the NLRP3-IL-1β axis in 5 UM and 4 CM cell lines. Expression of NLRP3 mRNA in UM and CM was low, and expression in UM was lower than in CM (P < 0.001). NLRP3 protein levels were below detection limit for all cell lines. UM exhibited lower baseline IL-1β secretion than CM, especially when compared to the Hs294t cell line (P < 0.05). Bioinformatic analysis of human tumor samples showed that UM has significantly lower expression of NLRP3 and IL-1β compared with CM. In conclusion, our work shows evidence of extremely low NLRP3 expression and IL-1β secretion by melanoma cells and highlight differences between CM and UM.
葡萄膜黑色素瘤 (UM) 是成年人中最常见的原发性眼内肿瘤。最近的研究表明,NLRP3 炎性体可能是皮肤黑色素瘤 (CM) 的治疗靶点,但 NLRP3 在 UM 中的作用尚不清楚。在这里,我们分析了 5 种 UM 和 4 种 CM 细胞系中的 NLRP3-IL-1β 轴。UM 和 CM 中 NLRP3 mRNA 的表达水平较低,且 UM 中的表达水平低于 CM(P<0.001)。所有细胞系的 NLRP3 蛋白水平均低于检测下限。UM 显示出比 CM 更低的基础 IL-1β 分泌水平,与 Hs294t 细胞系相比尤为明显(P<0.05)。对人类肿瘤样本的生物信息学分析表明,与 CM 相比,UM 中 NLRP3 和 IL-1β 的表达水平显著降低。综上所述,我们的工作表明黑色素瘤细胞 NLRP3 的表达和 IL-1β 的分泌极低,并突出了 CM 和 UM 之间的差异。