Paduch Roman, Klatka Maria, Pieniądz Paulina, Wertel Iwona, Pawłowska Anna, Klatka Janusz
Department of Virology and Immunology, Institute of Biological Sciences, Faculty of Biology and Biotechnology, Maria Curie-Skłodowska University, Akademicka 19, 20-033 Lublin, Poland.
Department of General and Paediatric Ophthalmology, Medical University of Lublin, Chmielna 1, 20-079 Lublin, Poland.
Curr Issues Mol Biol. 2024 Jul 2;46(7):6836-6852. doi: 10.3390/cimb46070408.
The tumor microenvironment (TME) includes immune and stromal cells and noncellular extracellular matrix (ECM) components. Tumor-associated macrophages (TAMs) are the most important immune cells in TME and are crucial for carcinomas' progression. The purpose was to analyze direct and indirect interactions in co-culture of tumor cells with monocytes/macrophages and, additionally, to indicate which interactions are more important for cancer development. Cytokines, reactive oxygen species, nitric oxide level, tumor cell cycle and changes in tumor cell morphology after human tumor cells (Hep-2 and RK33 cell lines) with human monocyte/macrophage (THP-1 cell line) interactions were tested. Morphology and cytoskeleton organization of tumor cells did not change after co-culture with macrophages. In co-culture of tumor cells with human monocyte, changes in the percentage of tumor cells in cell cycle phases was observed. No significant changes in reactive oxygen species (ROS) were found in the co-culture as compared to the tumor cell mono-culture. Monocytes produced about three times higher ROS than tumor cells. In co-cultures, a lower nitric oxide (NO) level was found as compared to the sum of the production by both mono-cultures. Co-culture conditions limited the production of cytokines (IL-4, IL-10 and IL-13) as compared to the sum of their level in mono-cultures. In conclusion, macrophages influence tumor cell growth and functions. Mutual (direct and paracrine) interactions between tumor cells and macrophages changed cytokine production and tumor cell cycle profile. The data obtained may allow us to initially indicate which kind of interactions may have a greater impact on cancer development processes.
肿瘤微环境（TME）包括免疫细胞、基质细胞以及无细胞的细胞外基质（ECM）成分。肿瘤相关巨噬细胞（TAM）是TME中最重要的免疫细胞，对癌症进展至关重要。本研究旨在分析肿瘤细胞与单核细胞/巨噬细胞共培养中的直接和间接相互作用，并指出哪些相互作用对癌症发展更为重要。检测了人肿瘤细胞（Hep-2和RK33细胞系）与人单核细胞/巨噬细胞（THP-1细胞系）相互作用后细胞因子、活性氧、一氧化氮水平、肿瘤细胞周期及肿瘤细胞形态的变化。肿瘤细胞与巨噬细胞共培养后，其形态和细胞骨架组织未发生改变。肿瘤细胞与人单核细胞共培养时，观察到细胞周期各阶段肿瘤细胞百分比的变化。与肿瘤细胞单培养相比，共培养中活性氧（ROS）无显著变化。单核细胞产生的ROS约为肿瘤细胞的三倍。与两种单培养物产生量之和相比，共培养中一氧化氮（NO）水平较低。与单培养物中细胞因子（IL-4、IL-10和IL-13）水平之和相比，共培养条件限制了细胞因子的产生。总之，巨噬细胞影响肿瘤细胞的生长和功能。肿瘤细胞与巨噬细胞之间的相互（直接和旁分泌）作用改变了细胞因子的产生和肿瘤细胞周期谱。所获得的数据可能使我们初步指出哪种相互作用可能对癌症发展过程有更大影响。
