Ding Lei, Wu Ling, Cao Yuting, Wang Hao, Li Defang, Chen Weibin, Huang Ping, Jiang Zengxin
Department of Orthopedic Surgery, Fudan University Jinshan Hospital, Shanghai, China.
Center for Joint Surgery, Department of Orthopedic Surgery, The Second Affiliated Hospital of Chongqing Medical University, Linjiang road No.76, Yuzhong District, Chongqing, China.
J Orthop Surg Res. 2024 Jul 31;19(1):453. doi: 10.1186/s13018-024-04950-2.
Osteosarcoma is a primary bone tumor lacking optimal clinical treatment options. Tumor-associated macrophages in the tumor microenvironment are closely associated with tumor development and metastasis. Studies have identified the macrophage receptor with collagenous structure (MARCO) as a specific receptor expressed in macrophages. This study aimed to investigate whether anti-MARCO mAb treatment can induce macrophage polarization in the tumor microenvironment and elicit anti-tumor effects.
THP-1 cells were treated with 20 ng/mL phorbol 12-myristate 13-acetate and 80 ng/mL interleukin-4 for 48 h to induce macrophage polarization to alternatively activated macrophages (M2). Enzyme-linked immunosorbent assay, real-time quantitative polymerase chain reaction, flow cytometry, and bioinformatic analyses were performed to evaluate macrophage polarization. The co-culture groups included a blank group, an M2 macrophage and U2OS co-culture group, and an anti-MARCO mAb-treated M2 macrophage group. Cell viability assays, cell scratch tests, apoptosis, and cell cycle analyses were performed to determine the effects of anti-MARCO mAb-treated macrophages on osteosarcoma cells.
It was demonstrated that anti-MARCO mAb can drive macrophages toward classically activated macrophage (M1) polarization. Anti-MARCO mAb promoted the secretion of pro-inflammatory factors by macrophages, including tumor necrosis factor-alpha (TNF-α), interleukin-1beta, interleukin-6 and interleukin-23. Studies on in vitro co-culture models have revealed that macrophages treated with anti-MARCO mAb can suppress the growth and migration of osteosarcoma cells, induce cell apoptosis, and inhibit cell cycle progression of osteosarcoma cells through M1 polarization of macrophages in vitro.
Anti-MARCO mAb treatment exerts anti-osteosarcoma effects by affecting macrophage polarization toward M1 macrophages, offering a potential new therapeutic approach for treating osteosarcoma.
骨肉瘤是一种缺乏最佳临床治疗方案的原发性骨肿瘤。肿瘤微环境中的肿瘤相关巨噬细胞与肿瘤的发生发展及转移密切相关。研究已确定具有胶原结构的巨噬细胞受体（MARCO）是巨噬细胞中表达的一种特异性受体。本研究旨在探讨抗MARCO单克隆抗体治疗是否能诱导肿瘤微环境中的巨噬细胞极化并引发抗肿瘤作用。
用20 ng/mL佛波酯12 - 肉豆蔻酸酯13 - 乙酸酯和80 ng/mL白细胞介素-4处理THP - 1细胞48小时，以诱导巨噬细胞极化为交替活化巨噬细胞（M2）。进行酶联免疫吸附测定、实时定量聚合酶链反应、流式细胞术和生物信息学分析以评估巨噬细胞极化。共培养组包括空白组、M2巨噬细胞与U2OS共培养组以及抗MARCO单克隆抗体处理的M2巨噬细胞组。进行细胞活力测定、细胞划痕试验、凋亡和细胞周期分析，以确定抗MARCO单克隆抗体处理的巨噬细胞对骨肉瘤细胞的影响。
结果表明，抗MARCO单克隆抗体可促使巨噬细胞向经典活化巨噬细胞（M1）极化。抗MARCO单克隆抗体促进巨噬细胞分泌促炎因子，包括肿瘤坏死因子-α（TNF-α）、白细胞介素-1β、白细胞介素-6和白细胞介素-23。体外共培养模型研究表明，抗MARCO单克隆抗体处理的巨噬细胞可通过体外巨噬细胞的M1极化抑制骨肉瘤细胞的生长和迁移，诱导细胞凋亡，并抑制骨肉瘤细胞的细胞周期进程。
抗MARCO单克隆抗体治疗通过影响巨噬细胞向M1巨噬细胞极化发挥抗骨肉瘤作用，为骨肉瘤治疗提供了一种潜在的新治疗方法。
