Alemán Omar Rafael, Quintero Juan Carlos, Camacho-Arroyo Ignacio
Unidad de Investigación en Reproducción Humana, Instituto Nacional de Perinatología-Facultad de Química, Universidad Nacional Autónoma de México, Mexico City 11000, México.
Neurooncol Adv. 2025 Jan 25;7(1):vdaf017. doi: 10.1093/noajnl/vdaf017. eCollection 2025 Jan-Dec.
Glioblastoma (GB) is the most aggressive and frequent tumor in the central nervous system and, in humans, represents the worst prognosis for cancer. GB develops a very complex microenvironment, recruiting and interacting with a variety of cells and soluble factors, including immune cells, cytokines, and sex hormones, that contribute to GB survival and progression. Recent evidence has shown a crosstalk between cytokine and sex hormone signaling in GB. This communication could provide GB resistance to treatments and malignancy. Then, how GB orchestrates this communication is a matter of interest. For instance, a critical interaction between tumor necrosis factor-beta (TGF-β) and estrogen receptor signaling has been reported in regulating epithelial-mesenchymal transition, an essential step in GB progression. Furthermore, an inhibition of TGF-β signaling by androgen receptor has been reported to promote GB tumorigenesis in men. Conversely, it has been described that cytokines regulate steroid hormone production in different organs, and this mechanism could be involved in GB development and progression. All these data suggest an intercommunication between the immune and endocrine systems in the tumor microenvironment. Thus, in this review, we focus on explaining the knowledge about this critical intercommunication system and its implication in GB progression.
胶质母细胞瘤（GB）是中枢神经系统中最具侵袭性且最为常见的肿瘤，在人类中，它代表着癌症的最差预后。GB会形成非常复杂的微环境，与多种细胞和可溶性因子相互作用，这些细胞和因子包括免疫细胞、细胞因子和性激素，它们都有助于GB的存活和进展。最近的证据表明，GB中细胞因子和性激素信号之间存在相互作用。这种相互作用可能使GB产生治疗抗性并导致恶性发展。那么，GB如何协调这种相互作用就成为了一个有趣的问题。例如，据报道肿瘤坏死因子-β（TGF-β）与雌激素受体信号之间的关键相互作用在调节上皮-间质转化过程中发挥作用，而上皮-间质转化是GB进展中的一个关键步骤。此外，据报道雄激素受体对TGF-β信号的抑制作用可促进男性GB的肿瘤发生。相反，已有研究表明细胞因子可调节不同器官中类固醇激素的产生，这种机制可能与GB的发生和进展有关。所有这些数据都表明肿瘤微环境中免疫和内分泌系统之间存在相互联系。因此，在本综述中，我们着重解释关于这一关键相互联系系统的知识及其在GB进展中的意义。
