Gutiérrez-Hoya Adriana, Ortiz-Garrido Ivan, Salazar-Valencia Itzel, Romero-Hernández Christopher, Valle-Mendiola Arturo, Weiss-Steider Benny, Soto-Cruz Isabel
Molecular Oncology Laboratory, Cell Differentiation and Cancer Research Unit, UMIEZ Campus II FES Zaragoza, National Autonomous University of Mexico, Mexico City 09230, Mexico.
Researcher CONAHCYT, Consejo Nacional de Humanidades, Ciencias y Tecnologías, Col. Crédito Constructor, Benito Juárez, Mexico City 03940, Mexico.
Biomolecules. 2024 Dec 1;14(12):1543. doi: 10.3390/biom14121543.
Cervical cancer is a global health problem; therapies focused on eliminating tumour cells and strengthening different immunotherapies are in development. However, it has been observed that cervical tumour cells can evade cell death mechanisms and generate immune system molecules to promote their proliferation and metastasis. In this context, we analysed the role of the IL-2 and CD95 pathways, essential molecules in activating the immune system and eliminating tumour cells. However, it is important to analyse their role in cervical tumour cells because these cells could be using these pathways to proliferate. In this study, we found that SiHa and HeLa cells respond to treatment, with 10 IU/mL of IL-2 inducing their proliferation and 100 IU/mL of IL-2 decreasing their proliferation. We also observed that they express a high percentage of the CD95 receptor and its ligand (CD95L) and that treatment with CD95 agonist antibodies at low doses increases cell proliferation. Furthermore, simultaneous treatment with high doses of IL-2 plus CD95 agonist antibody positively regulates LC3B accumulation. We did not observe apoptosis under any of the treatments carried out. In conclusion, cervical tumour cells can use the IL-2 and CD95 pathways to induce their proliferation and potentially activate cytoprotective mechanisms for survival.
宫颈癌是一个全球性的健康问题;旨在消除肿瘤细胞并加强不同免疫疗法的治疗方法正在研发中。然而,据观察,宫颈肿瘤细胞能够逃避细胞死亡机制,并产生免疫系统分子以促进其增殖和转移。在此背景下,我们分析了白细胞介素 -2(IL-2)和CD95途径的作用,它们是激活免疫系统和消除肿瘤细胞的关键分子。然而,分析它们在宫颈肿瘤细胞中的作用很重要,因为这些细胞可能利用这些途径进行增殖。在本研究中,我们发现SiHa和HeLa细胞对治疗有反应,10国际单位/毫升的IL-2会诱导其增殖,而100国际单位/毫升的IL-2会降低其增殖。我们还观察到它们表达高比例的CD95受体及其配体(CD95L),并且低剂量的CD95激动剂抗体处理会增加细胞增殖。此外,高剂量的IL-2与CD95激动剂抗体同时处理可正向调节微管相关蛋白1轻链3β(LC3B)的积累。在我们进行的任何处理下均未观察到细胞凋亡。总之,宫颈肿瘤细胞可以利用IL-2和CD95途径诱导其增殖,并可能激活细胞保护机制以实现存活。