Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Madrid, Spain.
Department of Biochemistry and Molecular Biology, Instituto Universitario de Investigación Neuroquímica (IUIN), Complutense University, Madrid, Spain.
Glia. 2023 Jan;71(1):127-138. doi: 10.1002/glia.24173. Epub 2022 Mar 24.
High-grade gliomas constitute the most frequent and aggressive form of primary brain cancer in adults. These tumors express cannabinoid CB and CB receptors, as well as other elements of the endocannabinoid system. Accruing preclinical evidence supports that pharmacological activation of cannabinoid receptors located on glioma cells exerts overt anti-tumoral effects by modulating key intracellular signaling pathways. The mechanism of this cannabinoid receptor-evoked anti-tumoral activity in experimental models of glioma is intricate and may involve an inhibition not only of cancer cell survival/proliferation, but also of invasiveness, angiogenesis, and the stem cell-like properties of cancer cells, thereby affecting the complex tumor microenvironment. However, the precise biological role of the endocannabinoid system in the generation and progression of glioma seems very context-dependent and remains largely unknown. Increasing our basic knowledge on how (endo)cannabinoids act on glioma cells could help to optimize experimental cannabinoid-based anti-tumoral therapies, as well as the preliminary clinical testing that is currently underway.
高级别神经胶质瘤是成人原发性脑癌中最常见且侵袭性最强的一种。这些肿瘤表达大麻素 CB1 和 CB2 受体以及其他内源性大麻素系统元件。越来越多的临床前证据表明，位于神经胶质瘤细胞上的大麻素受体的药理学激活通过调节关键的细胞内信号通路，对肿瘤发挥明显的抗肿瘤作用。在神经胶质瘤实验模型中，这种大麻素受体诱发的抗肿瘤活性的机制复杂，可能不仅涉及抑制癌细胞的存活/增殖，还涉及抑制侵袭、血管生成和癌细胞的干细胞样特性，从而影响复杂的肿瘤微环境。然而，内源性大麻素系统在神经胶质瘤的发生和进展中的精确生物学作用似乎非常依赖于具体情况，并且在很大程度上仍然未知。增加我们对内源性大麻素系统对神经胶质瘤细胞作用的基本认识，有助于优化基于大麻素的抗肿瘤实验治疗，以及目前正在进行的初步临床测试。
