Visualizing the Endothelial Glycocalyx in Human Glioma Vasculature

Overview

Journal Brain Tumor Pathol

Specialties Neurology
Oncology
Pathology

Date 2025 Mar 4

PMID 40035915

Authors

Kazufumi Ohmura

Hiroyuki Tomita

Hideshi Okada

Noriyuki Nakayama

Naoyuki Ohe

Tsuyoshi Izumo

Akira Hara

Affiliations

Soon will be listed here.

Abstract

Gliomas are the most common primary brain tumors in adults. However, glioblastoma is especially difficult to treat despite advancements in treatment. Therefore, new and more effective treatments are needed. The endothelial glycocalyx covers the luminal surface of the endothelium and plays an important role in vascular homeostasis. Tumor blood vessels normally have increased permeability, but some of them mimic normal cerebral blood vessels constituting the blood-brain barrier and retain drug-barrier function. Therefore, brain tumor vessels are considered to constitute the blood-tumor barrier. There are few reports on the endothelial glycocalyx in human brain tumor vessels. We aimed to visualize the endothelial glycocalyx in human brain tumor vessels and evaluate its microstructural differences in glioma vessels and normal capillaries. Surgical specimens from patients with glioma who underwent tumor resection at our institution were evaluated. We visualized the microstructures of the brain tumor vessels in human glioma specimens using electron microscopy with lanthanum nitrate. The endothelial glycocalyx was identified in the human glioma vasculature and its microstructure varied between the tumor margin and core. These variations may influence tumor angiogenesis and vascular remodeling, contributing to advancements in targeted therapies and diagnostics for human gliomas.

References

Hardee M, Zagzag D . Mechanisms of glioma-associated neovascularization. Am J Pathol. 2012; 181(4):1126-41. PMC: 3463636. DOI: 10.1016/j.ajpath.2012.06.030. View

Fu M, Zhou Z, Huang X, Chen Z, Zhang L, Zhang J . Use of Bevacizumab in recurrent glioblastoma: a scoping review and evidence map. BMC Cancer. 2023; 23(1):544. PMC: 10265794. DOI: 10.1186/s12885-023-11043-6. View

Belykh E, Shaffer K, Lin C, Byvaltsev V, Preul M, Chen L . Blood-Brain Barrier, Blood-Brain Tumor Barrier, and Fluorescence-Guided Neurosurgical Oncology: Delivering Optical Labels to Brain Tumors. Front Oncol. 2020; 10:739. PMC: 7290051. DOI: 10.3389/fonc.2020.00739. View

Arvanitis C, Ferraro G, Jain R . The blood-brain barrier and blood-tumour barrier in brain tumours and metastases. Nat Rev Cancer. 2019; 20(1):26-41. PMC: 8246629. DOI: 10.1038/s41568-019-0205-x. View

Hirano A, Matsui T . Vascular structures in brain tumors. Hum Pathol. 1975; 6(5):611-21. DOI: 10.1016/s0046-8177(75)80045-1. View

Shibata S . Ultrastructure of capillary walls in human brain tumors. Acta Neuropathol. 1989; 78(6):561-71. DOI: 10.1007/BF00691283. View

Vorbrodt A, Dobrogowska D . Molecular anatomy of intercellular junctions in brain endothelial and epithelial barriers: electron microscopist's view. Brain Res Brain Res Rev. 2003; 42(3):221-42. DOI: 10.1016/s0165-0173(03)00177-2. View

Hahn R, Patel V, Dull R . Human glycocalyx shedding: Systematic review and critical appraisal. Acta Anaesthesiol Scand. 2021; 65(5):590-606. DOI: 10.1111/aas.13797. View

Guven G, P Hilty M, Ince C . Microcirculation: Physiology, Pathophysiology, and Clinical Application. Blood Purif. 2019; 49(1-2):143-150. PMC: 7114900. DOI: 10.1159/000503775. View

10.

Ando Y, Okada H, Takemura G, Suzuki K, Takada C, Tomita H . Brain-Specific Ultrastructure of Capillary Endothelial Glycocalyx and Its Possible Contribution for Blood Brain Barrier. Sci Rep. 2018; 8(1):17523. PMC: 6269538. DOI: 10.1038/s41598-018-35976-2. View

11.

Offeddu G, Hajal C, Foley C, Wan Z, Ibrahim L, Coughlin M . The cancer glycocalyx mediates intravascular adhesion and extravasation during metastatic dissemination. Commun Biol. 2021; 4(1):255. PMC: 7910477. DOI: 10.1038/s42003-021-01774-2. View

12.

Tondepu C, Karumbaiah L . Glycomaterials to Investigate the Functional Role of Aberrant Glycosylation in Glioblastoma. Adv Healthc Mater. 2021; 11(4):e2101956. PMC: 9048137. DOI: 10.1002/adhm.202101956. View

13.

Kuliesiute U, Joseph K, Straehle J, Ravi V, Kueckelhaus J, Kada Benotmane J . Sialic acid metabolism orchestrates transcellular connectivity and signaling in glioblastoma. Neuro Oncol. 2023; 25(11):1963-1975. PMC: 10628944. DOI: 10.1093/neuonc/noad101. View

14.

Kinoshita T, Tomita H, Okada H, Niwa A, Hyodo F, Kanayama T . Endothelial cell-specific reduction of heparan sulfate suppresses glioma growth in mice. Discov Oncol. 2021; 12(1):50. PMC: 8585801. DOI: 10.1007/s12672-021-00444-3. View

15.

Reitsma S, Slaaf D, Vink H, van Zandvoort M, Oude Egbrink M . The endothelial glycocalyx: composition, functions, and visualization. Pflugers Arch. 2007; 454(3):345-59. PMC: 1915585. DOI: 10.1007/s00424-007-0212-8. View

16.

Princivalle M, de Agostini A . Developmental roles of heparan sulfate proteoglycans: a comparative review in Drosophila, mouse and human. Int J Dev Biol. 2002; 46(3):267-78. View

17.

Wang X, Kochi N, Tani E, Kaba K, Matsumoto T, Shindo H . Lectin histochemistry of human gliomas. Acta Neuropathol. 1989; 79(2):176-82. DOI: 10.1007/BF00294376. View

18.

Enomoto T, Okada H, Tomita H, Iinuma K, Nakane K, Tobisawa Y . Glycocalyx analysis of bladder cancer: three-dimensional images in electron microscopy and vicia villosa lectin as a marker for invasiveness in frozen sections. Front Cell Dev Biol. 2024; 11:1308879. PMC: 10806140. DOI: 10.3389/fcell.2023.1308879. View

19.

Suzuki A, Tomita H, Okada H . Form follows function: The endothelial glycocalyx. Transl Res. 2022; 247:158-167. DOI: 10.1016/j.trsl.2022.03.014. View

20.

Okada H, Takemura G, Suzuki K, Oda K, Takada C, Hotta Y . Three-dimensional ultrastructure of capillary endothelial glycocalyx under normal and experimental endotoxemic conditions. Crit Care. 2017; 21(1):261. PMC: 5651619. DOI: 10.1186/s13054-017-1841-8. View