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Ferroptosis induction inhibits metastasis formation in the metastatic uveal melanoma zebrafish model. A Western blot analysis determining GPX4, SLC7A11 and BAP1 protein expression in the two established cell lines MM66 and MM 46 and eight patient-derived tissues. Loading control: vinculin. Note, while BAP1 and GPX4 show a negative correlation in the patient samples, SLC7A11 was barely detected, independent of BAP1 expression levels. B, B’ Westernblot quantification of BAP1, SLC7A11 and GPX4. C qPCR analysis of GPX4 mRNA expression in primary UM tissues and spXmm66 (green dots), with known BAP1 status. Expression values were normalized to GAPDH (ΔCT). n = 3. D Quantitative analysis of tumor burden in the here established metastatic uveal melanoma zebrafish model. The indicated cells were engrafted at 48 hpf, maintained for 6 days in the absence or presence of the ferroptosis inducer erastin (SLC7A11 inhibitor, 5 μM) or RSL3 (GPX4 inhibitor, 10 μM) and subsequently subjected to tumor burden analysis. Notably, ferroptosis induction via erastin and/or RSL3 resulted in 4 out of 5 cases in a significant reduction of tumor burden. n = 40 (spXmm66) or n = 20 (all other cases). Data are mean ± SD. D3: chromosome 3 disomy: M3: chromosome 3 monosomy. ns: not significant. ***:p < 0.001.
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