Thomaz Amanda, Jaeger Mariane, Brunetto Algemir L, Brunetto André T, Gregianin Lauro, de Farias Caroline Brunetto, Ramaswamy Vijay, Nör Carolina, Taylor Michael D, Roesler Rafael
Cancer and Neurobiology Laboratory, Experimental Research Center, Clinical Hospital (CPE-HCPA), Federal University of Rio Grande do Sul, Porto Alegre 90035-003, RS, Brazil.
Department of Pharmacology, Institute for Basic Health Sciences, Federal University of Rio Grande do Sul, Porto Alegre 90050-170, RS, Brazil.
Cancers (Basel). 2020 Sep 7;12(9):2542. doi: 10.3390/cancers12092542.
Neurotrophins are a family of secreted proteins that act by binding to tropomyosin receptor kinase (Trk) or p75NTR receptors to regulate nervous system development and plasticity. Increasing evidence indicates that neurotrophins and their receptors in cancer cells play a role in tumor growth and resistance to treatment. In this review, we summarize evidence indicating that neurotrophin signaling influences medulloblastoma (MB), the most common type of malignant brain cancer afflicting children. We discuss the potential of neurotrophin receptors as new therapeutic targets for the treatment of MB. Overall, activation of TrkA and TrkC types of receptors seem to promote cell death, whereas TrkB might stimulate MB growth, and TrkB inhibition displays antitumor effects. Importantly, we show analyses of the gene expression profile of neurotrophins and their receptors in MB primary tumors, which indicate, among other findings, that higher levels of or are associated with reduced overall survival (OS) of patients with SHH MB tumors.
神经营养因子是一类分泌蛋白，通过与原肌球蛋白受体激酶（Trk）或p75NTR受体结合发挥作用，以调节神经系统的发育和可塑性。越来越多的证据表明，癌细胞中的神经营养因子及其受体在肿瘤生长和治疗抗性中发挥作用。在本综述中，我们总结了表明神经营养因子信号传导影响髓母细胞瘤（MB）的证据，髓母细胞瘤是困扰儿童的最常见类型的恶性脑癌。我们讨论了神经营养因子受体作为MB治疗新靶点的潜力。总体而言，TrkA和TrkC型受体的激活似乎促进细胞死亡，而TrkB可能刺激MB生长，并且抑制TrkB显示出抗肿瘤作用。重要的是，我们展示了对MB原发性肿瘤中神经营养因子及其受体基因表达谱的分析，其中除其他发现外，表明较高水平的 或 与SHH MB肿瘤患者的总生存期（OS）降低相关。
