Abstract:
Korean mistletoe (Viscum album L. var. coloratum) is renowned for its medicinal properties, including anti-cancer and immunoadjuvant effects. This study aimed to elucidate the mechanisms by which Korean mistletoe lectin (V. album L. var. coloratum agglutinin; VCA) modulates breast cancer cell apoptosis and macrophage polarization. The specific objectives were to (1) investigate the direct effects of VCA on MCF-7 breast cancer cells and THP-1-derived M1/M2 macrophages; (2) analyze the impact of VCA on the paracrine interactions between these cell types; and (3) compare the efficacy of VCA in 2D vs. 3D co-culture models to bridge the gap between in vitro and in vivo studies. We employed both 2D and 3D models, co-culturing human M1/M2 macrophages with human MCF-7 breast cancer cells in a Transwell system. Our research demonstrated that M1 and M2 macrophages significantly influenced the immune and apoptotic responses of breast cancer cells when exposed to VCA. M1 macrophages exhibited cytotoxic characteristics and enhanced VCA-induced apoptosis in both 2D and 3D co-culture models. Conversely, M2 macrophages initially displayed a protective effect by reducing apoptosis in breast cancer cells, but this protective effect was reversed upon exposure to VCA. Furthermore, our findings illustrate VCA\'s ability to modulate M1 and M2 polarization in breast cancer cells. Finally, the use of magnetic 3D cell cultures suggests their potential to yield results comparable to conventional 2D cultures, bridging the gap between in vitro and in vivo studies.
摘要:
韩国槲寄生(Viscum专辑L.var。coloratum)以其药用特性而闻名,包括抗癌和免疫佐剂作用。本研究旨在阐明韩国槲寄生凝集素(V.专辑L.var.彩色凝集素;VCA)调节乳腺癌细胞凋亡和巨噬细胞极化。具体目标是(1)研究VCA对MCF-7乳腺癌细胞和THP-1衍生的M1/M2巨噬细胞的直接影响;(2)分析VCA对这些细胞类型之间旁分泌相互作用的影响;(3)比较VCA在2D和3D共培养模型弥合了体外和体内研究之间的差距。我们采用了2D和3D模型,在Transwell系统中共培养人M1/M2巨噬细胞与人MCF-7乳腺癌细胞。我们的研究表明,当暴露于VCA时,M1和M2巨噬细胞显着影响乳腺癌细胞的免疫和凋亡反应。在2D和3D共培养模型中,M1巨噬细胞表现出细胞毒性特征和增强的VCA诱导的细胞凋亡。相反,M2巨噬细胞最初通过减少乳腺癌细胞凋亡而表现出保护作用,但这种保护作用在暴露于VCA时逆转。此外,我们的发现说明了VCA调节乳腺癌细胞M1和M2极化的能力。最后,磁性3D细胞培养的使用表明它们有可能产生与传统2D培养相当的结果,弥合体外和体内研究之间的差距。