Anaplastic thyroid carcinoma (ATC) is the most lethal subtype of thyroid cancer, with high invasive and metastatic potential, not responding to conventional treatments. Its aggressiveness may be influenced by macrophages, which are abundant cells in the tumor microenvironment. To investigate the role of macrophages in ATC aggressiveness, indirect co-cultures were established between ATC cell lines and THP-1-derived macrophages. Macrophages significantly increased both the migration and invasion of T235 cells (p< 0.01;p< 0.01), contrasting with a decrease in C3948 (p< 0.001;p< 0.05), with mild effects in T238 migration (p< 0.01) and C643 invasion (p< 0.05). Flow cytometry showed upregulation of CD80 (pro-inflammatory, anti-tumoral) and downregulation of CD163 (anti-inflammatory, pro-tumoral) in macrophages from co-culture with T235 (p< 0.05) and C3948 (p< 0.05), respectively. Accordingly, we found an upregulation of secreted pro-inflammatory mediators (e.g., GM-CSF, IL-1α;p< 0.05) in C3948–macrophage co-cultures. Proteomic analysis showed the upregulation of SPRY4, an inhibitor of the MAPK pathway, in C3948 cells from co-culture.SPRY4silencing promoted cancer cell invasion, reverting the reduced invasion of C3948 caused by macrophages. Our findings support that macrophages play a role in ATC cell aggressiveness.SPRY4is a possible modulator of macrophage–ATC cell communication, with a tumor suppressor role relevant for therapeutic purposes.
未分化甲状腺癌（ATC）是甲状腺癌中致死率最高的亚型，具有高度侵袭和转移潜能，且对常规治疗无反应。其侵袭性可能受肿瘤微环境中大量存在的巨噬细胞影响。为探究巨噬细胞在ATC侵袭性中的作用，本研究建立了ATC细胞系与THP-1来源巨噬细胞的间接共培养体系。结果显示，巨噬细胞显著促进T235细胞的迁移和侵袭能力（p<0.01；p<0.01），但抑制C3948细胞的迁移和侵袭（p<0.001；p<0.05），对T238细胞迁移（p<0.01）和C643细胞侵袭（p<0.05）的影响较弱。流式细胞术检测发现，与T235共培养的巨噬细胞中促炎抗肿瘤标志物CD80表达上调（p<0.05），而与C3948共培养的巨噬细胞中抗炎促肿瘤标志物CD163表达下调（p<0.05）。相应地，在C3948-巨噬细胞共培养体系中检测到分泌型促炎介质（如GM-CSF、IL-1α；p<0.05）表达上调。蛋白质组学分析显示，共培养后的C3948细胞中MAPK通路抑制因子SPRY4表达上调。沉默SPRY4可促进癌细胞侵袭，逆转巨噬细胞对C3948细胞侵袭的抑制作用。本研究证实巨噬细胞参与调控ATC细胞侵袭性，SPRY4可能是巨噬细胞-ATC细胞通讯的潜在调节因子，其抑癌作用为治疗策略提供了新方向。
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