Vasculogenic Mimicry Occurs at Low Levels in Primary and Recurrent Glioblastoma

Author:

Maddison Kelsey123,Faulkner Sam12ORCID,Graves Moira C.234,Fay Michael25,Bowden Nikola A.34ORCID,Tooney Paul A.123ORCID

Affiliation:

1. School of Biomedical Sciences and Pharmacy, The University of Newcastle, Callaghan, NSW 2308, Australia

2. Mark Hughes Foundation Centre for Brain Cancer Research, The University of Newcastle, Callaghan, NSW 2308, Australia

3. Drug Repurposing and Medicines Research Program, Hunter Medical Research Institute, New Lambton Heights, NSW 2305, Australia

4. School of Medicine and Public Health, The University of Newcastle, Callaghan, NSW 2308, Australia

5. GenesisCare, Lake Macquarie Private Hospital, Gateshead, NSW 2290, Australia

Abstract

Vasculogenic mimicry (VM), the ability of tumour cells to form functional microvasculature without an endothelial lining, may contribute to anti-angiogenic treatment resistance in glioblastoma. We aimed to assess the extent of VM formation in primary and recurrent glioblastomas and to determine whether VM vessels also express prostate-specific membrane antigen (PSMA), a pathological vessel marker. Formalin-fixed paraffin-embedded tissue from 35 matched pairs of primary and recurrent glioblastoma was immunohistochemically labelled for PSMA and CD34 and stained with periodic acid–Schiff (PAS). Vascular structures were categorised as endothelial vessels (CD34+/PAS+) or VM (CD34−/PAS+). Most blood vessels in both primary and recurrent tumours were endothelial vessels, and these significantly decreased in recurrent tumours (p < 0.001). PSMA was expressed by endothelial vessels, and its expression was also decreased in recurrent tumours (p = 0.027). VM was observed in 42.86% of primary tumours and 28.57% of recurrent tumours. VM accounted for only a small proportion of the tumour vasculature and VM density did not differ between primary and recurrent tumours (p = 0.266). The functional contribution of VM and its potential as a treatment target in glioblastoma require further investigation.

Funder

Mark Hughes Foundation Innovation

University of Newcastle HDR Scholarship

Australian Centre for Cannabinoid Clinical and Research Excellence

Vanessa McGuigan HMRI Mid-Career Fellowship in Ovarian Cancer

Publisher

MDPI AG

Subject

Cancer Research,Oncology

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