摘要
背景:多形性成胶质细胞瘤(GBM)是在成年中最常见的脑瘤并且具有较低的存活率。肿瘤微环境的不一致性、耐药性、放射治疗以及它较强的侵略性都导致了不良后果。大量的与小神经胶质和巨噬细胞相关的成胶质瘤细胞(GAMs)能够在肿瘤发生的地方积累,这在预后中具有重要的作用。 方法:关于该主题现有文献使用PubMed数据库进行了广泛的修订,本文探索了小神经胶质和巨噬细胞相关的成胶质瘤细胞到多形性成胶质细胞瘤生物学的贡献以及有证据显示小神经胶质和巨噬细胞相关的成胶质细胞瘤可以被药物调控抑制肿瘤细胞的增长。 结果:小神经胶质和巨噬细胞相关的成胶质细胞瘤占据整个脑胶质瘤质量的30%,是最大的一个部分。与肿瘤细胞相互作用后,GAMs获得一个独特的激活表型,包括M1和M2特异性标记物。不同的激活类型通常共存于同一个以来GAM位置或者病理状态的肿瘤中。除了调控可能控制或者倾向于形成星形胶质细胞恶性转化的免疫应答外,GAMs直接参与细胞外基质降解,这是一种可以扩大肿瘤和实质侵犯的重要的机制。目前已经发展了几种药理学的方法,包括干扰GAM在肿瘤部位、细胞分化和免疫功能方面的聚集,并通过GAM重塑ECM分泌因子。最有前途的治疗方法似乎是以GBM和GAM生物学特征为研究目标。 结论:GAMs明显有助于GAM生物学研究(倾向于肿瘤的生长和侵略)。本文所综述的数据表明这些细胞代表一个有价值的替代或者附加的靶点为GBM开发更多有效的治疗。
关键词: 成胶质细胞,小神经角质,巨噬细胞,M1,M2,NOS2,ARG-1,金属蛋白
Current Cancer Drug Targets
Title:Exploiting Microglial Functions for the Treatment of Glioblastoma
Volume: 17 Issue: 3
关键词: 成胶质细胞,小神经角质,巨噬细胞,M1,M2,NOS2,ARG-1,金属蛋白
摘要: Background: Glioblastoma multiforme (GBM) is the most common brain tumor in adults and is associated with a very low survival rate. The heterogeneity of the tumor microenvironment, its resistance to drug and radiation therapy, and its robust invasiveness all contribute to the poor outcome. Large numbers of glioma associated microglia and macrophages (GAMs) can accumulate within the tumor where they appear to have an important role in prognosis.
Methods: An extensive revision of current available literature on this topic has been carried out, using the PubMed database. Articles exploring the contribution of GAMs to GBM biology as well as evidence that GAMs can be pharmacologically modulated to inhibit tumor growth are critically discussed in this review article. Results: GAMs constitute the largest portion of tumor infiltrating cells contributing up to 30% of the entire glioma mass. Upon interaction with neoplastic cells, GAMs acquire a unique phenotype of activation including both M1 and M2 specific markers. Different profiles of activation usually co-exist in the same tumor that is dependent upon GAM location or stage of disease. In addition to regulating immune responses which may control or favor astrocyte malignant transformation, GAMs are directly involved in the degradation of the extracellular matrix (ECM), a crucial mechanism that allows the expansion of tumors and parenchyma invasion. Several pharmacological strategies have been developed which interfere with GAM recruitment at the tumor site, cell polarization and immune function, and ECM remodeling by GAM-secreted factors. The most promising therapeutic approaches appear to target both GBM cells and GAM biological properties. Conclusion: GAMs significantly contribute to GBM biology (favoring tumor growth and invasiveness). Data reviewed in the present article suggest that these cells represent a valuable alternative/ additional target for the development of more effective treatments for GBM.Export Options
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Cite this article as:
Exploiting Microglial Functions for the Treatment of Glioblastoma, Current Cancer Drug Targets 2017; 17 (3) . https://dx.doi.org/10.2174/1568009616666160813191240
DOI https://dx.doi.org/10.2174/1568009616666160813191240 |
Print ISSN 1568-0096 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-5576 |
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Cancer biomarkers play a crucial role in the diagnosis, prognosis, and treatment of cancer. They provide valuable information for cancer detection, risk assessment, treatment selection, and monitoring response to therapy. With advancements in molecular biology and high-throughput technologies, there has been an increasing interest in identifying and characterizing cancer biomarkers ...read more
Novel Therapeutic Approaches to Target Drug Resistant Tumors
With the development of disciplines such as chemical biology and molecular biology, the genes or proteins closely related to tumor occurrence and development have gradually become clear. Targeted therapies targeting these genes or proteins provide more effective methods for tumor treatment. Tumor targeted drugs generally only act on specific targets ...read more
ROLE OF IMMUNE AND GENOTOXIC RESPONSE BIOMARKERS IN TUMOR MICROENVIRONMENT IN CANCER DIAGNOSIS AND TREATMENT
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Immune system protects host against malignant tumors through effector cells and molecules. Cancer development and its response to therapy are regulated by inflammation, which either promotes or suppresses cancer progression. Chronic inflammation facilitates cancer progression and treatment resistance, whereas induction of acute inflammatory reactions often lead to anti-cancer immune responses. ...read more
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