Institute of Human Genetics, Diagnostic and Research Center for Molecular BioMedicine, Medical University of Graz, Graz, Austria.
Institute of Biology, Leiden University, Leiden, The Netherlands.
Sci Rep. 2019 Mar 11;9(1):4096. doi: 10.1038/s41598-019-40570-1.
Melanoma is a leading cause of high mortality that frequently spreads to the brain and is associated with deterioration in quality and quantity of life. Treatment opportunities have been restricted until now and new therapy options are urgently required. Our focus was to reveal the potential heterogeneity of melanoma brain metastasis. We succeeded to establish a brain melanoma metastasis cell line, namely MUG-Mel1 and two resulting clones D5 and C8 by morphological variety, differences in lipidome, growth behavior, surface, and stem cell markers. Mutation analysis by next-generation sequencing, copy number profiling, and cytogenetics demonstrated the different genetic profile of MUG-Mel1 and clones. Tumorigenicity was unsuccessfully tested in various mouse systems and finally established in a zebra fish model. As innovative treatment option, with high potential to pass the blood-brain barrier a peptide isolated from lactoferricin was studied in potential toxicity. Brain metastases are a major clinical challenge, therefore the development of relevant in vitro and in vivo models derived from brain melanoma metastases provides valuable information about tumor biology and offers great potential to screen for new innovative therapies.
黑色素瘤是导致高死亡率的主要原因，常发生脑转移，且与生活质量和数量的恶化有关。到目前为止，治疗机会有限，迫切需要新的治疗选择。我们的重点是揭示黑色素瘤脑转移的潜在异质性。我们成功地建立了脑黑色素瘤转移细胞系，即 MUG-Mel1 及其两个衍生克隆 D5 和 C8，其特征是形态学多样性、脂质组学差异、生长行为、表面和干细胞标志物不同。下一代测序、拷贝数分析和细胞遗传学的突变分析表明，MUG-Mel1 和克隆具有不同的遗传特征。在各种小鼠系统中未能成功测试肿瘤生成能力，最终在斑马鱼模型中建立。作为一种有潜力穿透血脑屏障的创新治疗选择，我们研究了从乳铁蛋白中分离出的肽的潜在毒性。脑转移是一个主要的临床挑战，因此，源自脑黑色素瘤转移的相关体外和体内模型的开发提供了有关肿瘤生物学的宝贵信息，并为筛选新的创新疗法提供了巨大潜力。
