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IQGAP1, AmotL2, and FKBP51 Scaffoldins in the Glioblastoma Microenvironment.
Journal of Histochemistry & Cytochemistry ( IF 1.9 ) Pub Date : 2019-02-22 , DOI: 10.1369/0022155419833334
Deborah Rotoli 1, 2, 3, 4, 5 , Manuel Morales 5, 6, 7 , María-Del-C Maeso 5, 8 , Julio Ávila 1, 2, 3 , Natalia D Pérez-Rodríguez 5, 6 , Ali Mobasheri 9 , Cornelis J F van Noorden 10, 11, 12 , Pablo Martín-Vasallo 1, 2, 3
Affiliation  

Glioblastoma (GB) is the most frequently occurring and aggressive primary brain tumor. Glioma stem cells (GSCs) and astrocytoma cells are the predominant malignant cells occurring in GB besides a highly heterogeneous population of migrating, neovascularizing and infiltrating myeloid cells that forms a complex tumor microenvironment (TME). Cross talk between the TME cells is pivotal in the biology of this tumor and, consequently, adaptor proteins at critical junctions of signaling pathways may be crucial. Scaffold proteins (scaffolins or scaffoldins) integrate external and internal stimuli to regulate various signaling pathways, interacting simultaneously with multiple proteins involved. We investigated by double and triple immunofluorescence the localization of IQGAP1, AmotL2, and FKBP51, three closely related scaffoldins, in malignant cells and TME of human GB tumors. We found that IQGAP1 is preferentially expressed in astrocytoma cells, AmotL2 in GSCs, and FKBP51 in white blood cells in human GB tumors. As GSCs are specially the target for novel therapies, we will investigate in further studies whether AmotL2 inhibition is effective in the treatment of GB.

中文翻译:

胶质母细胞瘤微环境中的IQGAP1,AmotL2和FKBP51支架蛋白。

胶质母细胞瘤(GB)是最常见和侵略性的原发性脑肿瘤。胶质瘤干细胞(GSC)和星形细胞瘤细胞是GB中最主要的恶性细胞,除了高度异质的迁移,新血管形成和浸润性髓样细胞群外,还形成复杂的肿瘤微环境(TME)。TME细胞之间的串扰在该肿瘤的生物学中至关重要,因此,信号通路关键连接处的衔接蛋白可能至关重要。支架蛋白(支架蛋白或支架蛋白)整合了外部和内部刺激,以调节各种信号传导途径,同时与涉及的多种蛋白质相互作用。我们通过两次和三次免疫荧光研究了三个密切相关的支架蛋白IQGAP1,AmotL2和FKBP51的定位,在人GB肿瘤的恶性细胞和TME中的表达。我们发现IQGAP1在星形细胞瘤细胞,GSC中的AmotL2和人GB肿瘤的白细胞中的FKBP51中优先表达。由于GSC特别是新疗法的靶标,因此我们将在进一步的研究中研究AmotL2抑制在GB的治疗中是否有效。
更新日期:2019-11-01
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