Neil Emily, Kouskoff Valerie
School of Medical Sciences, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester M13 9PT, UK.
Cancers (Basel). 2023 May 31;15(11):3005. doi: 10.3390/cancers15113005.
Epithelioid haemangioendothelioma (EHE) is a rare sarcoma of the vascular endothelium with an unpredictable disease course. EHE tumours can remain indolent for long period of time but may suddenly evolve into an aggressive disease with widespread metastases and a poor prognosis. Two mutually exclusive chromosomal translocations define EHE tumours, each involving one of the transcription co-factors TAZ and YAP. The TAZ-CAMTA1 fusion protein results from a t(1;3) translocation and is present in 90% of EHE tumours. The remaining 10% of EHE cases harbour a t(X;11) translocation, resulting in the YAP1-TFE3 (YT) fusion protein. Until recently, the lack of representative EHE models made it challenging to study the mechanisms by which these fusion proteins promote tumorigenesis. Here, we describe and compare the recently developed experimental approaches that are currently available for studying this cancer. After summarising the key findings obtained with each experimental approach, we discuss the advantages and limitations of these different model systems. Our survey of the current literature shows how each experimental approach can be utilised in different ways to improve our understanding of EHE initiation and progression. Ultimately, this should lead to better treatment options for patients.
上皮样血管内皮瘤(EHE)是一种罕见的血管内皮肉瘤,疾病进程不可预测。EHE肿瘤可能长期保持惰性,但也可能突然演变为侵袭性疾病,出现广泛转移且预后不良。两种相互排斥的染色体易位可定义EHE肿瘤,每种易位都涉及转录辅因子TAZ和YAP中的一种。TAZ-CAMTA1融合蛋白由t(1;3)易位产生,存在于90%的EHE肿瘤中。其余10%的EHE病例存在t(X;11)易位,产生YAP1-TFE3(YT)融合蛋白。直到最近,由于缺乏具有代表性的EHE模型,研究这些融合蛋白促进肿瘤发生的机制具有挑战性。在此,我们描述并比较了目前可用于研究这种癌症的最新开发的实验方法。在总结每种实验方法获得的关键发现后,我们讨论了这些不同模型系统的优缺点。我们对当前文献的调查表明,每种实验方法如何以不同方式用于增进我们对EHE起始和进展的理解。最终,这应该为患者带来更好的治疗选择。