Cancer Research Program, Research Institute of the McGill University Health Centre, Montreal, QC, Canada; The MUHC - McGill University Ocular Pathology & Translational Research Laboratory, Montreal, QC, Canada.
Cancer Research Program, Research Institute of the McGill University Health Centre, Montreal, QC, Canada; The MUHC - McGill University Ocular Pathology & Translational Research Laboratory, Montreal, QC, Canada.
Exp Eye Res. 2024 Nov;248:110120. doi: 10.1016/j.exer.2024.110120. Epub 2024 Oct 9.
Uveal Melanoma (UM) is the most common primary intraocular malignancy in adults. Although rare, it is a deadly tumor, with a long-term prognosis of death occurring in more than 50% of the cases. It is characterized by frequent (∼80%) driver mutations in GNAQ and GNA11 genes, both of which are activated by cysteinyl leukotriene receptors (CYSLTRs). CYSLTR1 is upregulated and participated in the progression of several cancers. In the present study, we sought to determine the expression levels of CYSLTR1 in 31 human UM specimens and cell lines (3 primary and 1 metastatic), and its role in the proliferation and viability of these cells by analyzing cell metabolic activity, cell confluence and apoptosis levels. We show that all analyzed UM specimens and cells expressed CYSLTR1 at high levels. Notably, the pharmacological blockage of this receptor, using the inverse agonist MK571, reduced the growth and metabolic activity, and increased the apoptotic cell death of all analyzed UM cell lines. We provide evidence that CYSLTR1 is expressed in human UM and plays a significant role in UM progression behavior. Our data highlight the potential beneficial effects of targeting CYSLTR1 in the control of UM progression.
葡萄膜黑色素瘤（UM）是成年人中最常见的原发性眼内恶性肿瘤。尽管罕见，但它是一种致命的肿瘤，超过 50%的病例长期预后为死亡。其特征是 GNAQ 和 GNA11 基因频繁（约 80%）发生驱动突变，这两个基因均被半胱氨酰白三烯受体（CYSLTRs）激活。CYSLTR1 上调并参与了几种癌症的进展。在本研究中，我们试图确定 31 个人 UM 标本和细胞系（3 个原发和 1 个转移）中 CYSLTR1 的表达水平，并通过分析细胞代谢活性、细胞汇合度和细胞凋亡水平来确定其在这些细胞增殖和活力中的作用。我们表明，所有分析的 UM 标本和细胞均高水平表达 CYSLTR1。值得注意的是，使用反向激动剂 MK571 阻断该受体可降低所有分析的 UM 细胞系的生长和代谢活性，并增加凋亡性细胞死亡。我们提供的证据表明 CYSLTR1 在人 UM 中表达，并在 UM 进展行为中发挥重要作用。我们的数据强调了靶向 CYSLTR1 控制 UM 进展的潜在有益效果。
