Tang Yujun, Luo Jie, Jiang Bin, Deng Jian, Li Jiehua, Qin Liuqing
Department of Plastic, The Second Affiliated Hospital of the University of South China, University of South China, Hengyang, 421001, China.
Department of Gastrointestinal Glandular, The First Affiliated Hospital of Guangxi Medical University, Guangxi Medical University, Nanning, 530021, China.
In Vitro Cell Dev Biol Anim. 2025 Jul 2. doi: 10.1007/s11626-025-01066-7.
This study aimed to investigate the role of mesenchymal homeobox 2 (MEOX2) on breast cancer cell metastasis and its underlying mechanism. Overexpression of MEOX2 in human lymphatic endothelial cell (HLEC) lines was established to assess the adhesion and transendothelial migration of MCF7 and MDA-MB-231 cells to the HLEC cells. After being treated with the oxidative stress inducer HO and the antioxidant N-acetylcysteine (NAC), cell viability, reactive oxygen species (ROS) levels, adhesion, and transendothelial migration of MCF7 and MDA-MB-231 cells to HLEC cells were detected. Tumor volume changes were observed in the xenograft model. The expression of C-X-C chemokine receptor type 4 (CXCR4), C-C chemokine receptor type 7 (CCR7), MEOX2, and G protein signal transduction regulator 5 (RGS5) in tumor tissues and ROS levels were detected. MEOX2 was lowly expressed in breast cancer tissues. Upregulated MEOX2 inhibited the proliferation of lymphatic endothelial cells and the adhesion and transendothelial migration of MCF7 and MDA-MB-231 cells to HLEC cells. After MCF7 and MDA-MB-231 cells were treated with oxidative stress inducer HO, ROS levels increased, and cell viability and MEOX2 expression decreased. After NAC or overexpressed MEOX2 treatment, MEOX2 expression increased, ROS and RGS5 levels, adhesion, and transendothelial migration ability decreased in HLEC cells. Overexpression of MEOX2 resulted in smaller tumor volume, lower ROS levels, and lower CXCR4 and CCR7 expression levels. MEOX2 and RGS5 are pivotal in regulating breast cancer metastasis, offering valuable insights into potential therapeutic strategies for breast cancer metastasis.
本研究旨在探讨间充质同源框2（MEOX2）在乳腺癌细胞转移中的作用及其潜在机制。通过在人淋巴管内皮细胞（HLEC）系中建立MEOX2过表达模型，以评估MCF7和MDA-MB-231细胞与HLEC细胞的黏附及跨内皮迁移能力。在用氧化应激诱导剂HO和抗氧化剂N-乙酰半胱氨酸（NAC）处理后，检测MCF7和MDA-MB-231细胞的细胞活力、活性氧（ROS）水平、与HLEC细胞的黏附及跨内皮迁移能力。在异种移植模型中观察肿瘤体积变化。检测肿瘤组织中C-X-C趋化因子受体4（CXCR4）、C-C趋化因子受体7（CCR7）、MEOX2和G蛋白信号转导调节因子5（RGS5）的表达以及ROS水平。MEOX2在乳腺癌组织中低表达。上调MEOX2可抑制淋巴管内皮细胞的增殖以及MCF7和MDA-MB-231细胞与HLEC细胞的黏附及跨内皮迁移。MCF7和MDA-MB-231细胞经氧化应激诱导剂HO处理后，ROS水平升高，细胞活力和MEOX2表达降低。经NAC或过表达MEOX2处理后，HLEC细胞中MEOX2表达增加，ROS和RGS5水平、黏附及跨内皮迁移能力降低。MEOX2过表达导致肿瘤体积减小、ROS水平降低以及CXCR4和CCR7表达水平降低。MEOX2和RGS5在调节乳腺癌转移中起关键作用，为乳腺癌转移的潜在治疗策略提供了有价值的见解。
