Laboratory of Molecular and Cellular Biology (LIM 15), Department of Neurology, Faculdade de Medicina FMUSP, Universidade de Sao Paulo, Sao Paulo, Brasil.
PLoS One. 2018 Jun 18;13(6):e0199211. doi: 10.1371/journal.pone.0199211. eCollection 2018.
Toll-like receptors (TLRs) are the first to identify disturbances in the immune system, recognizing pathogens such as bacteria, fungi, and viruses. Since the inflammation process plays an important role in several diseases, TLRs have been considered potential therapeutic targets, including treatment for cancer. However, TLRs' role in cancer remains ambiguous. This study aims to analyze the expression levels of plasmatic cell membrane TLRs (TLR1, TLR2, TLR4, TLR5, and TLR6) in human astrocytomas the most prevalent tumors of CNS different grades (II-IV). We demonstrated that TLR expressions were higher in astrocytoma samples compared to non-neoplastic brain tissue. The gene and protein expressions were observed in GBM cell lines U87MG and A172, proving their presence in the tumor cells. Associated expressions between the known heterodimers TLR1-TLR2 were found in all astrocytoma grades. In GBMs, the mesenchymal subtype showed higher levels of TLR expressions in relation to classical and proneural subtypes. A strong association of TLRs with the activation of cell cycle process and signaling through canonical, inflammasome and ripoptosome pathways was observed by in silico analysis, further highlighting TLRs as interesting targets for cancer treatment.
Toll 样受体 (TLRs) 是最早识别免疫系统紊乱的受体,能够识别细菌、真菌和病毒等病原体。由于炎症过程在多种疾病中起着重要作用,TLRs 已被认为是潜在的治疗靶点,包括癌症治疗。然而,TLRs 在癌症中的作用仍存在争议。本研究旨在分析不同级别(II-IV)的人星形细胞瘤中浆细胞膜 TLRs(TLR1、TLR2、TLR4、TLR5 和 TLR6)的表达水平。我们证明了 TLR 在星形细胞瘤样本中的表达高于非肿瘤性脑组织。在 GBM 细胞系 U87MG 和 A172 中观察到基因和蛋白表达,证明了它们在肿瘤细胞中的存在。在所有星形细胞瘤级别中都发现了已知异二聚体 TLR1-TLR2 的相关表达。在 GBM 中,间充质亚型与经典和前神经亚型相比,TLR 表达水平更高。通过计算机分析观察到 TLRs 与细胞周期过程的激活以及通过经典、炎症小体和 ripoptosome 途径的信号转导之间存在强烈关联,进一步强调了 TLRs 作为癌症治疗的有趣靶点。