Uveal melanoma cell lines Mel270 and 92.1 exhibit a mesenchymal phenotype and sensitivity to the cytostatic effects of transforming growth factor beta in vitro

Purpose: 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-I3) 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-I3 pathway could be relevant in the treatment of metastatic UM. Methods: 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-I3 to evaluate their responsiveness to the cytokine and to characterize the functional impact of TGF-I3 on their cell viability. Results: The results demonstrated, first, that the UM cell lines exhibited a mesenchymal phenotype and responded to TGF-I3 treatment in vitro and, second, that TGF-I3 promoted a cytostatic effect on the UM cell lines. Conclusions: Our findings indicate that UM cells are sensitive to the two arms of TGF-I3 signaling, which suggests that targeting the TGF-I3 pathway could be challenging in UM and would require a precise selection of patients in which only the prometastatic arm of TGF-I3 is activated.