Mitrofanova Lubov, Hazratov Anton, Galkovsky Boris, Gorshkov Andrey, Bobkov Danila, Gulyaev Dmitry, Shlyakhto Evgeny
Almazov National Medical Research Centre, Pathomorphology Research Laboratory, St. Petersburg, Russia.
Smorodintsev Research Institute of Influenza, Laboratory of Intracellular Signaling and Transport, St. Petersburg, Russia.
Oncotarget. 2020 Jan 28;11(4):322-346. doi: 10.18632/oncotarget.27340.
Telocytes (Tcs) and pericytes (Pcs) are two types of perivascular interstitial cell known to be widespread in various organs and tissues, including the brain. We postulated that Tcs and Pcs may be involved in glioblastoma (GBM) neovascularization.
Morphological study of Tc and Pc roles in GBM.
Samples from 15 GBM, 10 diffuse astrocytoma, as well as 5 control samples were studied. We used immunohistochemistry (IHC) with antibodies (Abs) to GFAP, Ki-67, CD117, NeuroD1, NG2, CD34, and SMA. Confocal laser scanning microscopy (CLSM) of 4 glioma tissue cultures and 4 GBM sections was performed with GFAP, CD117, CD34/connexin43, NeuroD1/connexin43, CD34/NG2 and CD13/CD117 Abs. Electron microscopy (EM) of GBM was performed in 4 cases.
The presence of Tcs and Pcs was shown in GBM (IHC, EM, CLSM) and glioma cultures (CLSM). The Tc immunophenotype was CD117/CD34/connexin43/NeuroD1. The Pc immunophenotype was SMA/NG2/CD13. The number of Tcs in GBM specimens was 10 times higher than in astrocytoma. We also identified CD13/CD117 and CD34/NG2 co-expressing cells in GBM blood vessels.
Four immunophenotypes were found in GBM vessels, corresponding to endotheliocytes, Pcs, Tcs, and a mixed Pc/Tc immunophenotype. These and forthcoming improvements in our understanding of the origin and function of Tcs, including their relationship with Pcs, are necessary steps in oncology. Study of these cell types (Tcs, Pcs) and their roles in brain tumor oncogenesis will likely enable improved targeted therapies and support development of new forms of anti-neoplastic drugs.
端细胞(Tcs)和周细胞(Pcs)是两种已知广泛存在于包括脑在内的各种器官和组织中的血管周围间质细胞。我们推测Tcs和Pcs可能参与胶质母细胞瘤(GBM)的血管生成。
对Tcs和Pcs在GBM中的作用进行形态学研究。
研究了15例GBM、10例弥漫性星形细胞瘤以及5例对照样本。我们使用针对GFAP、Ki-67、CD117、NeuroD1、NG2、CD34和SMA的抗体进行免疫组织化学(IHC)。用针对GFAP、CD117、CD34/连接蛋白43、NeuroD1/连接蛋白43、CD34/NG2和CD13/CD117抗体对4例胶质瘤组织培养物和4例GBM切片进行共聚焦激光扫描显微镜(CLSM)检查。对4例GBM进行电子显微镜(EM)检查。
在GBM(IHC、EM、CLSM)和胶质瘤培养物(CLSM)中均显示存在Tcs和Pcs。Tc免疫表型为CD117/CD34/连接蛋白43/NeuroD1。Pc免疫表型为SMA/NG2/CD13。GBM标本中Tcs的数量比星形细胞瘤高10倍。我们还在GBM血管中鉴定出了共表达CD13/CD117和CD34/NG2的细胞。
在GBM血管中发现了四种免疫表型,分别对应内皮细胞、Pcs、Tcs以及混合的Pc/Tc免疫表型。这些以及我们对Tcs起源和功能(包括它们与Pcs的关系)理解的即将到来的进展,是肿瘤学中的必要步骤。对这些细胞类型(Tcs、Pcs)及其在脑肿瘤发生中的作用的研究可能会带来改进的靶向治疗,并支持新型抗肿瘤药物的开发。