Snuderl Matija, Zhang Guoan, Wu Pamela, Jennings Tara S, Shroff Seema, Ortenzi Valerio, Jain Rajan, Cohen Benjamin, Reidy Jason J, Dushay Mitchell S, Wisoff Jeffrey H, Harter David H, Karajannis Matthias A, Fenyo David, Neubert Thomas A, Zagzag David
Division of Neuropathology, Department of Pathology, New York University Langone Medical Center and Medical School, New York, New York; Department of Neurology, New York University Langone Medical Center and Medical School, New York, New York.
Department of Biochemistry and Molecular Pharmacology, New York University School of Medicine, New York, New York; Kimmel Center for Biology and Medicine at the Skirball Institute, New York University School of Medicine, New York, New York.
Am J Pathol. 2017 Aug;187(8):1867-1878. doi: 10.1016/j.ajpath.2017.04.004. Epub 2017 Jun 9.
Optic gliomas are brain tumors characterized by slow growth, progressive loss of vision, and limited therapeutic options. Optic gliomas contain various amounts of myxoid matrix, which can represent most of the tumor mass. We sought to investigate biological function and protein structure of the myxoid matrix in optic gliomas to identify novel therapeutic targets. We reviewed histological features and clinical imaging properties, analyzed vasculature by immunohistochemistry and electron microscopy, and performed liquid chromatography-mass spectrometry on optic gliomas, which varied in the amount of myxoid matrix. We found that although subtypes of optic gliomas are indistinguishable on imaging, the microvascular network of pilomyxoid astrocytoma, a subtype of optic glioma with abundant myxoid matrix, is characterized by the presence of endothelium-free channels in the myxoid matrix. These tumors show normal perfusion by clinical imaging and lack histological evidence of hemorrhage organization or thrombosis. The myxoid matrix is composed predominantly of the proteoglycan versican and its linking protein, a vertebrate hyaluronan and proteoglycan link protein 1. We propose that pediatric optic gliomas can maintain blood supply without endothelial cells by using invertebrate-like channels, which we termed primitive myxoid vascularization. Enzymatic targeting of the proteoglycan versican/hyaluronan and proteoglycan link protein 1 rich myxoid matrix, which is in direct contact with circulating blood, can provide novel therapeutic avenues for optic gliomas of childhood.
视神经胶质瘤是一种脑肿瘤，其特征为生长缓慢、视力逐渐丧失且治疗选择有限。视神经胶质瘤含有不同量的黏液样基质，黏液样基质可占肿瘤大部分体积。我们试图研究视神经胶质瘤中黏液样基质的生物学功能和蛋白质结构，以确定新的治疗靶点。我们回顾了组织学特征和临床影像学特性，通过免疫组织化学和电子显微镜分析了血管系统，并对黏液样基质含量不同的视神经胶质瘤进行了液相色谱 - 质谱分析。我们发现，尽管视神经胶质瘤的亚型在影像学上难以区分，但毛细胞黏液样星形细胞瘤（一种具有丰富黏液样基质的视神经胶质瘤亚型）的微血管网络特征是在黏液样基质中存在无内皮通道。这些肿瘤通过临床影像学显示灌注正常，且缺乏出血组织或血栓形成的组织学证据。黏液样基质主要由蛋白聚糖多功能蛋白聚糖及其连接蛋白（一种脊椎动物透明质酸和蛋白聚糖连接蛋白1）组成。我们提出，儿童视神经胶质瘤可通过使用类似无脊椎动物的通道来维持无内皮细胞情况下的血液供应，我们将这种通道称为原始黏液样血管生成。对与循环血液直接接触的富含蛋白聚糖多功能蛋白聚糖/透明质酸和蛋白聚糖连接蛋白1的黏液样基质进行酶靶向作用，可为儿童视神经胶质瘤提供新的治疗途径。
