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Am J Pathol. 2017 Aug;187(8):1867-1878. doi: 10.1016/j.ajpath.2017.04.004. Epub 2017 Jun 9.

Endothelium-Independent Primitive Myxoid Vascularization Creates Invertebrate-Like Channels to Maintain Blood Supply in Optic Gliomas.

Author information

1
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.
2
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.
3
Department of Biochemistry and Molecular Pharmacology, New York University School of Medicine, New York, New York; Institute of Systems Genetics, New York University Langone Medical Center, New York, New York.
4
Division of Neuropathology, Department of Pathology, New York University Langone Medical Center and Medical School, New York, New York.
5
Department of Radiology, New York University Langone Medical Center and Medical School, New York, New York; Department of Neurosurgery, New York University Langone Medical Center and Medical School, New York, New York.
6
Department of Radiology, New York University Langone Medical Center and Medical School, New York, New York.
7
Department of Pathology, Mount Sinai Beth Israel Medical Center, New York, New York.
8
Department of Entomology, Cornell University, Ithaca, New York.
9
Department of Neurosurgery, New York University Langone Medical Center and Medical School, New York, New York; Division of Pediatric Neurosurgery, New York University Langone Medical Center and Medical School, New York, New York.
10
Division of Pediatric Hematology/Oncology, Department of Pediatrics and Otolaryngology, New York University Langone Medical Center and Perlmutter Cancer Center, New York, New York.
11
Division of Neuropathology, Department of Pathology, New York University Langone Medical Center and Medical School, New York, New York; Department of Neurosurgery, New York University Langone Medical Center and Medical School, New York, New York; Microvascular and Molecular Neurooncology Laboratory, Department of Pathology, New York University Langone Medical Center, New York, New York. Electronic address: dz4@nyu.edu.

Abstract

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.

PMID:
28606795
PMCID:
PMC5530906
DOI:
10.1016/j.ajpath.2017.04.004
[Indexed for MEDLINE]
Free PMC Article

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