Angiogenesis in patient-derived xenografts of odontogenic myxoma

IF 1.8 4区 医学 Q3 PATHOLOGY International Journal of Experimental Pathology Pub Date : 2022-02-28 DOI:10.1111/iep.12431
Juliana Cristina de Souza, Victor Coutinho Bastos, Núbia Braga Pereira, Adriana Abalen Martins Dias, Gleide Fernandes de Avelar, Ricardo Santiago Gomez, Carolina Cavaliéri Gomes
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Abstract

Previously, by employing 3D organotypic tissue culture and patient-derived xenograft (PDX) model, oral myxoma response to a MAPK/MEK inhibitor was observed. Gross examination of the tumour fragments obtained after 55 days of PDX grafting revealed increased capsule vascularization. Microscopic analyses showed blood capillaries intermixed with myxoma cells, but the origin of these capillaries, from mice or humans, was not established. This study aimed to investigate whether the endothelial cells observed in the myxoma PDX model are derived from the mouse or from the primary human tumour. Immunohistochemistry was performed on five tumour fragments from the PDX of myxoma after 55 days of implantation in mice. Immunopositivity for antibodies against human (HLA-ABC) and mouse (H2 Db/H2-D1) major histocompatibility complex class I (MHCI) was assessed in the endothelial cells. The endothelial cells in the PDX fragments revealed a membrane staining for the human MHCI protein in the PDX tumour and adjacent connective tissue capsule, indicating that capillaries were derived from the human tumour fragment. Considering the probable human origin of the endothelial cells from capillary blood vessels in the myxoma PDX, we conclude that this PDX model is an interesting model to study myxoma angiogenesis.

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牙源性黏液瘤患者异种移植物的血管生成
此前,通过采用3D器官型组织培养和患者来源的异种移植(PDX)模型,观察了口腔黏液瘤对MAPK/MEK抑制剂的反应。PDX移植55天后肿瘤碎片的大体检查显示囊血管化增加。显微镜分析显示毛细血管与黏液瘤细胞混杂在一起,但这些毛细血管的来源,无论是小鼠还是人类,尚未确定。本研究旨在探讨在黏液瘤PDX模型中观察到的内皮细胞是来自小鼠还是来自原发人肿瘤。在小鼠黏液瘤植入55天后,对黏液瘤PDX的5个肿瘤片段进行免疫组化。检测内皮细胞抗人(HLA-ABC)和小鼠(H2 Db/H2- d1)主要组织相容性复合体I类(MHCI)抗体的免疫阳性。PDX片段中的内皮细胞在PDX肿瘤和邻近结缔组织囊中显示人MHCI蛋白的膜染色,表明毛细血管来源于人肿瘤片段。考虑到黏液瘤PDX的内皮细胞可能来源于人类毛细血管,我们认为PDX模型是研究黏液瘤血管生成的一个有趣的模型。
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来源期刊
CiteScore
4.50
自引率
3.30%
发文量
35
审稿时长
>12 weeks
期刊介绍: Experimental Pathology encompasses the use of multidisciplinary scientific techniques to investigate the pathogenesis and progression of pathologic processes. The International Journal of Experimental Pathology - IJEP - publishes papers which afford new and imaginative insights into the basic mechanisms underlying human disease, including in vitro work, animal models, and clinical research. Aiming to report on work that addresses the common theme of mechanism at a cellular and molecular level, IJEP publishes both original experimental investigations and review articles. Recent themes for review series have covered topics as diverse as "Viruses and Cancer", "Granulomatous Diseases", "Stem cells" and "Cardiovascular Pathology".
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