碘难治性甲状腺癌（RR-DTC）失分化导致其对131I治疗无效，病死率升高，急需寻求新的治疗手段。我们前期研究发现肿瘤相关巨噬细胞（TAM）能降低甲状腺癌细胞的分化能力，新近研究提示Wnt/β-catenin信号通路可能参与甲状腺癌失分化，而唑来膦酸能抑制TAM。预实验也检测到TAM较前体THP-1细胞表达更多的Wnt配体。基于上述工作基础，我们通过RT-PCR、western blot、免疫荧光、核素摄取等体外实验，小动物SPECT等体内实验以及临床病理标本检测三个水平研究TAM分泌Wnt配体，激活Wnt/β-catenin信号通路，导致甲状腺癌失分化，从而降低细胞摄碘能力的作用机制，为唑来膦酸干预TAM，确立RR-DTC的再分化治疗提供科学依据。

Dedifferentiation of differentiated thyroid carcinoma (DTC) represents a main cause of radioiodine refraction. Radioiodine-refractory DTC (RR-DTC) is currently incurable, leading to a much higher mortality. Our group has found that tumor-associated macrophage (TAM) impair differentiation in thyroid carcinoma cell. Recent studies suggest that Wnt/β-catenin pathway may have a role in differentiation of thyroid carcinoma, and zoledronic acid can inhibit TAM. We also have found that TAM induces the expression of Wnt ligands. The present study is designed to investigate the feasibility of TAM secretes Wnt ligands and impairs differentiation in thyroid carcinoma through an Wnt/β-catenin pathway, which may be inhibited by zoledronic acid. These effects and the underling mechanisms are evaluated using RT-PCR, western blot, immunofluorescence, radioiodine uptake assay, SPECT, IHC. Aiming at exploring a novel, re-differentiating therapy for the treatment of RR-DTC.