Disproportion in Pericyte/Endothelial Cell Proliferation and Mechanisms of Intussusceptive Angiogenesis Participate in Bizarre Vessel Formation in Glioblastoma.

Ibrahim González-Marrero,Lucio Díaz-Flores,Pablo Martín-Vasallo,Ricardo Gutiérrez,María-Del-Pino García,Julio Ávila,Miriam González-Gómez

doi:10.3390/cells10102625

Ibrahim González-Marrero, Lucio Díaz-Flores + Show 5 more

Open Access

https://doi.org/10.3390/cells10102625

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Journal: Cells	Publication Date: Oct 1, 2021
Citations: 8	License type: CC BY 4.0

Affiliation: University of La Laguna, Hospiten Group

Abstract

Glioblastoma (GBM) is the most malignant tumor in the brain. In addition to the vascular pattern with thin-walled vessels and findings of sprouting angiogenesis, GBM presents a bizarre microvasculature (BM) formed by vascular clusters, vascular garlands, and glomeruloid bodies. The mechanisms in BM morphogenesis are not well known. Our objective was to assess the role of pericyte/endothelial proliferation and intussusceptive angiogenic mechanisms in the formation of the BM. For this purpose, we studied specimens of 66 GBM cases using immunochemistry and confocal microscopy. In the BM, the results showed (a) transitional forms between the BM patterns, mostly with prominent pericytes covering all the abluminal endothelial cell (EC) surface of the vessels, (b) a proliferation index high in the prominent pericytes and low in ECs (47.85 times higher in pericytes than in ECs), (c) intravascular pillars (hallmark of intussusceptive angiogenesis) formed by transcapillary interendothelial bridges, endothelial contacts of opposite vessel walls, and vessel loops, and (d) the persistence of these findings in complex glomeruloid bodies. In conclusion, disproportion in pericyte/EC proliferation and mechanisms of intussusceptive angiogenesis participate in BM formation. The contributions have morphogenic and clinical interest since pericytes and intussusceptive angiogenesis can condition antiangiogenic therapy in GBM.

Highlights

Glioblastoma (GBM) is a highly malignant tumor with bizarre microvasculature (BM) [1,2,3,4]
In GBM, we studied the morphogenesis of the BM and report as main findings (a) disproportion in the pericyte/endothelial cell (EC)
We take into consideration (a) the vascular patterns in GBM, (b) the high proliferation of pericytes in relation to ECs, leading to pericyte hyperplasia and hypertrophy, and extension and thinning of ECs, and (c) the mechanisms of pillar formation and their participation in bizarre vessel morphogenesis

Summary

Introduction

Glioblastoma (GBM) is a highly malignant tumor with bizarre microvasculature (BM) [1,2,3,4]. The microvascular patterns in GBM include (a) thin-walled vessels with findings of microvascular sprouting (the “classic” vascular pattern), which is not the object of this study, (b) vascular clusters, (c) vascular garlands, and (d) glomeruloid bodies [1,2,3,4]. Glomeruloid bodies, the most complex and demonstrative of these bizarre vascular structures, are made up of closely packed anastomosing capillaries with irregular and tortuous, narrow lumina. Their main cell components are endothelial cells (ECs) and numerous pericytes [5,6,7]. Glomeruloid bodies can be observed in other conditions in the brain (e.g., cancer metastasis) [8], they are an important finding for GBM diagnosis

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