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头颈部副神经节瘤中成纤维细胞和巨噬细胞的功能分析

Functional analysis of fibroblasts and macrophages in head and neck paragangliomas.

作者信息

Baruah Paramita, Marshall Jennifer L, Nefla Meriam, Pucino Valentina, Adams Holly, Turner Jason D, Gilbert Sebastian, Powell Emily, Neag Georgiana, Monksfield Peter, Irving Richard M, Croft Adam P, Dumitriu Ingrid E, Buckley Christopher D

机构信息

Department of Ear Nose and Throat (ENT), University of Leicester National Health Service (NHS) Trust, Birmingham, United Kingdom.

Department of Ear Nose and Throat (ENT), Queen Elizabeth Hospital Birmingham, Birmingham, United Kingdom.

出版信息

Front Endocrinol (Lausanne). 2024 Nov 15;15:1397839. doi: 10.3389/fendo.2024.1397839. eCollection 2024.

DOI:10.3389/fendo.2024.1397839
PMID:39619326
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11604431/
Abstract

BACKGROUND AND AIM

Head and neck paragangliomas (HNPGN) are tumours that carry significant morbidity The role of the stroma in the pathogenesis of HNPGN is not completely understood. This study explores the profile of fibroblasts and macrophages in HNPGN.

METHODS

Ten patients undergoing HNPGN surgery were recruited. CD68 and CD163 immunohistochemistry was performed for macrophage analysis; CD90 and podoplanin (PDPN) expression was examined to identify fibroblasts. RT-qPCR was performed on HNPGN tissue for macrophage- and fibroblast-associated molecules. Fibroblast cultures were established from HNPGN were analysed by RT-qPCR and flowcytometry. Confocal microscopy for MCT1 and MCT4 was performed in HNPGN.

RESULTS

CD68 and CD163 expressing macrophages were noted in HNPGN. CD90 and PDPN expressing cells were present in HNPGN. RT-qPCR analysis showed expression of phenotypic and functional macrophage- and fibroblast-associated molecules in HNPGN. RT-qPCR analysis of fibroblasts cultured from HNPGN confirmed the expression of several molecules including PDPN at comparable levels to healthy tissue fibroblasts. Expression of FAP, MCT-1, insulin receptor (CD220) and insulin growth factor receptor-2 (CD222) was noted on HNPGN derived fibroblasts on flowcytometry. MCT1 and MCT4 were expressed in HNPGN tumour cells and stromal macrophages .

CONCLUSION

Fibroblasts and macrophages are present in the HNPGN tumour microenvironment, and several macrophage and fibroblast functional markers are expressed in HNPGN. Macrophages in HNPGN tissue express metabolic markers MCT1 and MCT4. Further analysis of the fibroblast and macrophage function in HNPGN will improve our understanding of their potential roles in tumour pathogenesis.

摘要

背景与目的

头颈部副神经节瘤（HNPGN）是具有显著发病率的肿瘤。基质在HNPGN发病机制中的作用尚未完全明确。本研究探讨HNPGN中 成纤维细胞和巨噬细胞的特征。

方法

招募10例行HNPGN手术的患者。进行CD68和CD163免疫组化以分析巨噬细胞；检测CD90和血小板内皮细胞黏附分子（PDPN）表达以鉴定成纤维细胞。对HNPGN组织进行逆转录定量聚合酶链反应（RT-qPCR）检测巨噬细胞和成纤维细胞相关分子。从HNPGN建立成纤维细胞培养物，通过RT-qPCR和流式细胞术进行分析。在HNPGN中进行MCT1和MCT4的共聚焦显微镜检查。

结果

在HNPGN中发现表达CD68和CD163的巨噬细胞。在HNPGN中存在表达CD90和PDPN的细胞。RT-qPCR分析显示HNPGN中存在表型和功能相关的巨噬细胞和成纤维细胞分子表达。对从HNPGN培养的成纤维细胞进行RT-qPCR分析，证实包括PDPN在内的几种分子的表达水平与健康组织成纤维细胞相当。流式细胞术检测发现HNPGN来源的成纤维细胞表达成纤维细胞活化蛋白（FAP）、单羧酸转运蛋白-1（MCT-1）、胰岛素受体（CD220）和胰岛素生长因子受体-2（CD222）。MCT1和MCT4在HNPGN肿瘤细胞和基质巨噬细胞中表达。

结论

成纤维细胞和巨噬细胞存在于HNPGN肿瘤微环境中，且HNPGN中表达多种巨噬细胞和成纤维细胞功能标志物。HNPGN组织中的巨噬细胞表达代谢标志物MCT1和MCT4。对HNPGN中成纤维细胞和巨噬细胞功能的进一步分析将增进我们对它们在肿瘤发病机制中潜在作用的理解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/15dc/11604431/7d0ca2d6c9cf/fendo-15-1397839-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/15dc/11604431/ffd11919f4ab/fendo-15-1397839-g001.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/15dc/11604431/260af79603a0/fendo-15-1397839-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/15dc/11604431/7d0ca2d6c9cf/fendo-15-1397839-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/15dc/11604431/ffd11919f4ab/fendo-15-1397839-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/15dc/11604431/c4a14a0d81db/fendo-15-1397839-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/15dc/11604431/2dc7f5edfdba/fendo-15-1397839-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/15dc/11604431/260af79603a0/fendo-15-1397839-g004.jpg
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