UD of Biochemistry and Molecular Biology.
Instituto de Tecnologías Biomédicas de Canarias.
J Histochem Cytochem. 2019 Jul;67(7):481-494. doi: 10.1369/0022155419833334. Epub 2019 Feb 22.
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.
胶质母细胞瘤（GB）是最常见和侵袭性最强的原发性脑肿瘤。除了高度异质的迁移、新生血管和浸润的髓样细胞外，神经胶质瘤干细胞（GSCs）和星形细胞瘤细胞是 GB 中主要的恶性细胞，形成了一个复杂的肿瘤微环境（TME）。TME 细胞之间的串扰在这种肿瘤的生物学中至关重要，因此，信号通路关键节点的衔接蛋白可能至关重要。支架蛋白（scaffolins 或 scaffoldins）将外部和内部刺激整合在一起，以调节各种信号通路，同时与多个涉及的蛋白质相互作用。我们通过双重和三重免疫荧光技术研究了三种密切相关的支架蛋白 IQGAP1、AmotL2 和 FKBP51 在人类 GB 肿瘤的恶性细胞和 TME 中的定位。我们发现 IQGAP1 在星形细胞瘤细胞中优先表达，AmotL2 在 GSCs 中表达，FKBP51 在人类 GB 肿瘤的白细胞中表达。由于 GSCs 是新型治疗的特别靶点，我们将在进一步的研究中探讨 AmotL2 抑制在 GB 治疗中的有效性。
