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Open Access 01-12-2020 | Cytokines | Original Article

The role of the tumour microenvironment in the angiogenesis of pituitary tumours

Authors: Pedro Marques, Sayka Barry, Eivind Carlsen, David Collier, Amy Ronaldson, Neil Dorward, Joan Grieve, Nigel Mendoza, Ramesh Nair, Samiul Muquit, Ashley B. Grossman, Márta Korbonits

Published in: Endocrine | Issue 3/2020

Abstract

Purpose

Angiogenesis has been studied in pituitary neuroendocrine tumours (PitNETs), but the role of the tumour microenvironment (TME) in regulating PitNET angiogenesis remains unknown. We aimed to characterise the role of TME components in determining the angiogenetic PitNET profile, focusing on immune cells and tumour-derived cytokines.

Methods

Immune cells were studied by immunohistochemistry in 24 human PitNETs (16 non-functioning-PitNETs (NF-PitNETs) and 8 somatotrophinomas): macrophages (CD68, CD163, HLA-DR), cytotoxic (CD8) and T helper (CD4) lymphocytes, regulatory T cells (FOXP3), B cells (CD20) and neutrophils (neutrophil elastase); endothelial cells were assessed with CD31. Five normal pituitaries (NP) were included for comparison. Microvessel density and vascular morphology were estimated with ImageJ. The cytokine secretome from these PitNETs were assessed on culture supernatants using a multiplex immunoassay panel.

Results

Microvessel density/area was higher in NP than PitNETs, which also had rounder and more regular vessels. NF-PitNETs had vessels of increased calibre compared to somatotrophinomas. The M2:M1 macrophage ratio correlated with microvessel area. PitNETs with more CD4+ T cells had higher microvessel area, while tumours with more FOXP3+ cells were associated with lower microvessel density. PitNETs with more B cells had rounder vessels. Of the 42 PitNET-derived cytokines studied, CCL2, CXCL10 and CX3CL1 correlated with microvessel density and vessel architecture parameters.

Conclusions

M2 macrophages appear to play a role in PitNET neovascularisation, while B, CD4+ and FOXP3+ lymphocytes, as well as non-cellular TME elements such as CCL2, CXCL10 and CX3CL1, may also modulate the angiogenesis of PitNETs.

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Title: The role of the tumour microenvironment in the angiogenesis of pituitary tumours
Authors: Pedro Marques
Sayka Barry
Eivind Carlsen
David Collier
Amy Ronaldson
Neil Dorward
Joan Grieve
Nigel Mendoza
Ramesh Nair
Samiul Muquit
Ashley B. Grossman
Márta Korbonits
Publication date: 01-12-2020
Publisher: Springer US
Keyword: Cytokines
Published in: Endocrine / Issue 3/2020
Print ISSN: 1355-008X
Electronic ISSN: 1559-0100
DOI: https://doi.org/10.1007/s12020-020-02478-z

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Keynote webinar | Spotlight on medication adherence

Springer Medicine

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Other articles of this Issue 3/2020

A missed case of pheochromocytoma in NF1 patient presenting as pre-eclampsia

Correction to: Efficacy of oral rosuvastatin intervention on HDL and its associated proteins in men with type 2 diabetes mellitus

Effectiveness of lanreotide autogel 120 mg at extended dosing intervals for acromegaly

Status and clinical and radiological predictive factors of presurgical anterior pituitary function in pituitary adenomas. Study of 232 patients

Long-term outcome of differentiated thyroid cancer in children and young adults: risk stratification by ATA criteria and assessment of pre-ablation stimulated thyroglobulin as predictors of disease persistence

Correction to: Malignant struma ovarii: next-generation sequencing of six cases revealed Nras, Braf, and Jak3 mutations

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