肿瘤相关巨噬细胞通过EGFR/ERK1/2调节的EMT促进甲状腺癌肺转移

Tumor-associated macrophages (TAMs) play an important role in accelerating cancer progression. Anaplastic thyroid cancer (ATC) contains a higher density of TAMs than differentiated thyroid cancer. This study aimed to investigate the mechanism of action of TAMs in ATC lung metastasis. TAMs biomarkers and EMT-related proteins were detected in ATC using immunohistochemistry and immunofluorescence staining. Then, direct and indirect co-culture systems of TAMs and ATC cells were established. EMT-related proteins and related signaling pathways in ATC cells of co-culture systems were measured by RT-PCR and Western blotting. Finally, in vitro and in vivo experiments using the ERK inhibitor U0126 inhibited the EMT process in ATC cells and the growth of metastatic tumors in the lungs of nude mice. The results indicate that the expression of EMT-related proteins is positively correlated with TAMs biomarkers and EGF released by TAMs plays an important role by activating ERK1/2. This suggests that TAMs can induce EMT in cancer cells by activating the EGFR/ERK1/2 signaling pathway in ATC, which may be a potential therapeutic strategy to inhibit ATC metastasis.

肿瘤相关巨噬细胞（TAMs）在加速癌症进展中起重要作用。相比分化型甲状腺癌，未分化型甲状腺癌（ATC）中含有较高的TAMs密度。本研究旨在探讨TAMs在ATC肺转移中的作用机制。在ATC中使用免疫组织化学和免疫荧光染色检测TAMs生物标志物和EMT相关蛋白。然后，建立了TAMs和ATC细胞的直接和间接共培养系统。通过RT-PCR和蛋白质印迹测量共培养系统的ATC细胞中的EMT相关蛋白和相关信号传导途径。最后，体外及体内实验应用ERK抑制剂U0126抑制了ATC细胞中的EMT过程和裸鼠肺内转移瘤生长。结果表明，EMT相关蛋白的表达与TAMs生物标志物呈正相关和由TAMs释放的EGF通过激活ERK1/2起重要作用。这表明TAMs可以通过激活ATC中的EGFR/ERK1/2信号传导通路诱导癌细胞的EMT，这可能是抑制ATC转移的潜在的治疗策略。

肿瘤相关巨噬细胞（TAMs）在加速癌症进展中起重要作用。相比分化型甲状腺癌，未分化型甲状腺癌（ATC）中含有较高的TAMs密度。本研究旨在探讨TAMs在ATC肺转移中的作用机制。在ATC中使用免疫组织化学检测TAMs生物标志物和EMT相关蛋白。然后，建立了TAMs和ATC细胞的直接和间接共培养系统。通过RT-PCR和蛋白质印迹测量共培养系统的ATC细胞中的EMT相关蛋白和相关信号传导途径。最后，体外及体内实验应用ERK抑制剂U0126抑制了ATC细胞中的EMT过程和裸鼠肺内转移瘤生长。结果表明，EMT相关蛋白的表达与TAMs生物标志物呈正相关和由TAMs释放的EGF通过激活ERK1/2起重要作用。这表明TAMs可以通过激活ATC中的EGFR/ERK1/2信号传导通路诱导癌细胞的EMT，这可能是抑制ATC转移的潜在的治疗策略。