Department of Bioscience and Bioengineering, Indian Institute of Technology Jodhpur, Old Residency Road, Jodhpur, Rajasthan, 342011, India.
Department of Bioscience and Bioengineering, Indian Institute of Technology Jodhpur, Old Residency Road, Jodhpur, Rajasthan, 342011, India.
Cytokine Growth Factor Rev. 2017 Apr;34:15-26. doi: 10.1016/j.cytogfr.2017.02.001. Epub 2017 Feb 9.
Gliomas are the most common solid tumors among central nervous system tumors. Most glioma patients succumb to their disease within two years of the initial diagnosis. The median survival of gliomas is only 14.6 months, even after aggressive therapy with surgery, radiation, and chemotherapy. Gliomas are heavily infiltrated with myeloid- derived cells and endothelial cells. Increasing evidence suggests that these myeloid- derived cells interact with tumor cells promoting their growth and migration. NLRs (nucleotide-binding oligomerization domain (NOD)-containing protein like receptors) are a class of pattern recognition receptors that are critical to sensing pathogen and danger associated molecular patterns. Mutations in some NLRs lead to autoinflammatory diseases in humans. Moreover, dysregulated NLR signaling is central to the pathogenesis of several cancers, autoimmune and neurodegenerative diseases. Our review explores the role of angiogenic factors that contribute to upstream or downstream signaling pathways leading to NLRs. Angiogenesis plays a significant role in the pathogenesis of variety of tumors including gliomas. Though NLRs have been detected in several cancers including gliomas and NLR signaling contributes to angiogenesis, the exact role and mechanism of involvement of NLRs in glioma angiogenesis remain largely unexplored. We discuss cellular, molecular and genetic studies of NLR signaling and convergence of NLR signaling pathways with angiogenesis signaling in gliomas. This may lead to re-appropriation of existing anti-angiogenic therapies or development of future strategies for targeted therapeutics in gliomas.
神经胶质瘤是中枢神经系统肿瘤中最常见的实体肿瘤。大多数神经胶质瘤患者在初始诊断后的两年内死于该疾病。即使经过手术、放疗和化疗等积极治疗，神经胶质瘤的中位生存期也只有 14.6 个月。神经胶质瘤大量浸润髓样细胞和内皮细胞。越来越多的证据表明，这些髓样细胞与肿瘤细胞相互作用，促进其生长和迁移。NLRs（核苷酸结合寡聚化结构域（NOD）样受体）是一类模式识别受体，对于识别病原体和危险相关分子模式至关重要。某些 NLRs 的突变会导致人类发生自身炎症性疾病。此外，NLR 信号失调是几种癌症、自身免疫和神经退行性疾病发病机制的核心。我们的综述探讨了血管生成因子在 NLRs 上游或下游信号通路中的作用。血管生成在多种肿瘤的发病机制中起着重要作用，包括神经胶质瘤。尽管 NLRs 已在几种癌症中被检测到，包括神经胶质瘤，并且 NLR 信号有助于血管生成，但 NLRs 在神经胶质瘤血管生成中的确切作用和机制在很大程度上仍未得到探索。我们讨论了 NLR 信号的细胞、分子和遗传研究，以及 NLR 信号通路与神经胶质瘤血管生成信号的融合。这可能导致重新利用现有的抗血管生成疗法或为神经胶质瘤的靶向治疗开发未来的策略。
