ERBB3:一种用于早期检测的潜在血清生物标志物及袋獾面部肿瘤1(DFT1)的治疗靶点。

ERBB3: A potential serum biomarker for early detection and therapeutic target for devil facial tumour 1 (DFT1).

作者信息

Hayes Dane A, Kunde Dale A, Taylor Robyn L, Pyecroft Stephen B, Sohal Sukhwinder Singh, Snow Elizabeth T

机构信息

Department of Primary Industries, Parks Water and Environment, Animal Health Laboratory, Launceston, Tasmania, Australia.

Save the Tasmanian Devil Program, University of Tasmania, Hobart, Tasmania, Australia.

出版信息

PLoS One. 2017 Jun 7;12(6):e0177919. doi: 10.1371/journal.pone.0177919. eCollection 2017.

Abstract

Devil Facial Tumour 1 (DFT1) is one of two transmissible neoplasms of Tasmanian devils (Sarcophilus harrisii) predominantly affecting their facial regions. DFT1's cellular origin is that of Schwann cell lineage where lesions are evident macroscopically late in the disease. Conversely, the pre-clinical timeframe from cellular transmission to appearance of DFT1 remains uncertain demonstrating the importance of an effective pre-clinical biomarker. We show that ERBB3, a marker expressed normally by the developing neural crest and Schwann cells, is immunohistohemically expressed by DFT1, therefore the potential of ERBB3 as a biomarker was explored. Under the hypothesis that serum ERBB3 levels may increase as DFT1 invades local and distant tissues our pilot study determined serum ERBB3 levels in normal Tasmanian devils and Tasmanian devils with DFT1. Compared to the baseline serum ERBB3 levels in unaffected Tasmanian devils, Tasmanian devils with DFT1 showed significant elevation of serum ERBB3 levels. Interestingly Tasmanian devils with cutaneous lymphoma (CL) also showed elevation of serum ERBB3 levels when compared to the baseline serum levels of Tasmanian devils without DFT1. Thus, elevated serum ERBB3 levels in otherwise healthy looking devils could predict possible DFT1 or CL in captive or wild devil populations and would have implications on the management, welfare and survival of Tasmanian devils. ERBB3 is also a therapeutic target and therefore the potential exists to consider modes of administration that may eradicate DFT1 from the wild.

摘要

袋獾面部肿瘤1型(DFT1)是袋獾(袋獾属袋獾)的两种可传播肿瘤之一,主要影响其面部区域。DFT1的细胞起源是施万细胞谱系,在疾病后期肉眼可见病变。相反,从细胞传播到DFT1出现的临床前时间框架仍不确定,这表明有效的临床前生物标志物很重要。我们发现,ERBB3是一种在发育中的神经嵴和施万细胞中正常表达的标志物,DFT1可通过免疫组化法检测到其表达,因此我们探索了ERBB3作为生物标志物的潜力。基于DFT1侵袭局部和远处组织时血清ERBB3水平可能升高的假设,我们的初步研究测定了正常袋獾和患有DFT1的袋獾的血清ERBB3水平。与未受影响的袋獾的基线血清ERBB3水平相比,患有DFT1的袋獾的血清ERBB3水平显著升高。有趣的是,与没有DFT1的袋獾的基线血清水平相比,患有皮肤淋巴瘤(CL)的袋獾的血清ERBB3水平也有所升高。因此,在外观看起来健康的袋獾中,血清ERBB3水平升高可能预示着圈养或野生袋獾种群中可能存在DFT1或CL,这将对袋獾的管理、福利和生存产生影响。ERBB3也是一个治疗靶点,因此有可能考虑采用能从野外根除DFT1的给药方式。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a8c5/5462353/535a97d6ffe9/pone.0177919.g001.jpg

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