Service d'Ophtalmologie, CHU Rennes, Rennes, France.
INSERM U1242, OSS, Université Rennes, Rennes, France.
Mol Vis. 2024 Mar 22;30:160-166. eCollection 2024.
Uveal melanoma (UM) is a deadly cancer with limited therapeutic options. At advanced stages, UM cells metastasize almost exclusively into the liver, where targeting metastatic UM cells remain a clinical challenge. Transforming growth factor beta (TGF-β) exhibits a functional duality in cancer, with one arm limiting tumor growth at an early stage and the second arm promoting metastasis at an advanced stage, notably by inducing an epithelial-to-mesenchymal transition. Thus, we hypothesized that targeting the TGF-β pathway could be relevant in the treatment of metastatic UM.
In this study, we first characterized the pseudoepithelial/mesenchymal phenotype of UM cell lines Mel270 and 92.1. We then treated the cell lines with TGF-β to evaluate their responsiveness to the cytokine and to characterize the functional impact of TGF-β on their cell viability.
The results demonstrated, first, that the UM cell lines exhibited a mesenchymal phenotype and responded to TGF-β treatment in vitro and, second, that TGF-β promoted a cytostatic effect on the UM cell lines.
Our findings indicate that UM cells are sensitive to the two arms of TGF-β signaling, which suggests that targeting the TGF-β pathway could be challenging in UM and would require a precise selection of patients in which only the prometastatic arm of TGF-β is activated.
葡萄膜黑色素瘤（UM）是一种致命的癌症，治疗选择有限。在晚期，UM 细胞几乎只转移到肝脏，而针对转移性 UM 细胞仍然是一个临床挑战。转化生长因子-β（TGF-β）在癌症中表现出功能双重性，一方面在早期限制肿瘤生长，另一方面在晚期促进转移，特别是通过诱导上皮-间充质转化。因此，我们假设靶向 TGF-β 途径可能与转移性 UM 的治疗有关。
在这项研究中，我们首先对 UM 细胞系 Mel270 和 92.1 的假上皮/间充质表型进行了特征描述。然后，我们用 TGF-β 处理这些细胞系，以评估它们对细胞因子的反应，并分析 TGF-β对它们细胞活力的功能影响。
结果首先表明，UM 细胞系表现出间充质表型，并对 TGF-β 处理在体外有反应，其次，TGF-β 促进了 UM 细胞系的细胞增殖抑制作用。
我们的发现表明，UM 细胞对 TGF-β 信号通路的两个分支敏感，这表明靶向 TGF-β 途径在 UM 中可能具有挑战性，并且需要对 TGF-β 的促转移分支被激活的患者进行精确选择。
