Placone Amanda L, Quiñones-Hinojosa Alfredo, Searson Peter C
Institute for Nanobiotechnology, Johns Hopkins University, 3400 North Charles Street, Baltimore, MD, 21218, USA.
Department of Materials Science and Engineering, Johns Hopkins University, 3400 North Charles Street, Baltimore, MD, 21218, USA.
Tumour Biol. 2016 Jan;37(1):61-9. doi: 10.1007/s13277-015-4242-0. Epub 2015 Oct 22.
Gliomas and brain-metastatic tumors contribute to hundreds of thousands of deaths every year. Typical survival times for brain cancer patients, even with surgical, chemotherapy, and radiation treatment, remain very low despite advances in treatment. In brain cancers, astrocytes, which comprise approximately 50 % of the cells in the brain, become activated, resulting in a layer of reactive astrocytes surrounding the tumor. This process of reactive gliosis, which involves the secretion of growth factors and cytokines, helps repair injury in the brain, but also plays a role in disease progression. In this review, we survey the mechanisms by which astrocytes modulate the local tumor microenvironment, enhancing proliferation, invasion, chemoprotection, and immunoprotection of tumor cells. Consideration of the effect of astrocytes and reactive gliosis in in vitro and in vivo assays may allow us to obtain a more complete picture of the interactions occurring at the tumor microenvironment, which will provide additional insight into potential pathways that can be targeted by brain cancer therapeutics.
神经胶质瘤和脑转移瘤每年导致数十万人死亡。尽管治疗取得了进展,但脑癌患者的典型生存时间仍然很低,即使接受了手术、化疗和放疗。在脑癌中,约占大脑细胞50%的星形胶质细胞被激活,导致肿瘤周围形成一层反应性星形胶质细胞。这种反应性胶质增生过程涉及生长因子和细胞因子的分泌,有助于修复脑损伤,但也在疾病进展中起作用。在这篇综述中,我们探讨了星形胶质细胞调节局部肿瘤微环境、增强肿瘤细胞增殖、侵袭、化学保护和免疫保护的机制。考虑星形胶质细胞和反应性胶质增生在体外和体内试验中的作用,可能使我们更全面地了解肿瘤微环境中发生的相互作用,这将为脑癌治疗可靶向的潜在途径提供更多见解。