癌相关成纤维细胞自噬对甲状腺乳头状癌影响的研究  

Role of cancer-associated fibroblasts autophagy in papillary thyroid cancer

作　　者：张雪梅[1,4] 孙丹阳 李宁[1] 张其成[3] 徐克 郑薇[1] 贾强[1] 谭建[1] 孟召伟[1] Zhang Xuemei;Sun Danyang;Li Ning;Zhang Qicheng;Xu Ke;Zheng Wei;Jia Qiang;Tan Jian;Meng Zhaowei(Department of Nuclear Medicine,Tianjin Medical University General Hospital,Tianjin 300052,China;Department of Nuclear Medicine,Tianjin Medical University General Hospital Airport Site,Tianjin 300308,China;Tianjin Lung Cancer Institute,Tianjin Medical University General Hospital,Tianjin 300052,China;Department of Radiology and Nuclear Medicine,Xuanwu Hospital,Beijing 100053)

机构地区：[1]天津医科大学总医院核医学科,天津300052 [2]天津医科大学总医院空港医院核医学科,天津300308 [3]天津医科大学总医院肺癌研究所,天津300052 [4]北京宣武医院放射与核医学科,北京100053

出　　处：《中华内分泌代谢杂志》2025年第2期135-144,共10页Chinese Journal of Endocrinology and Metabolism

基　　金：国家自然科学基金(81971650);天津市科学技术委员会基金(21JCYBJC01820)。

摘　　要：目的探讨癌相关成纤维细胞(cancer-associated fibroblasts,CAF)的自噬变化对甲状腺乳头状癌(papillary thyroid cancer,PTC)的影响。方法从4例PTC患者的癌灶和邻近正常甲状腺组织中分离出CAF和正常成纤维细胞。评估其中的成纤维细胞活化蛋白(fibroblast activation protein,FAP)和α-平滑肌肌动蛋白的表达。制备CAF条件培养基和正常成纤维细胞条件培养基并用于培养PTC细胞。通过细胞增殖实验、细胞划痕实验、细胞侵袭实验和细胞摄碘实验评估其对PTC细胞存活、增殖、迁移、侵袭和摄碘的影响。评估CAF自噬水平,自噬抑制及自噬激活后进一步评估其对PTC细胞增殖、迁移和侵袭的影响。荷瘤裸鼠动物实验明确CAF自噬对PTC移植瘤生长增殖的影响。结果与正常成纤维细胞相比,CAF中的FAP蛋白表达水平更高,且与CAF的条件培养基共培养的PTC细胞表现出更强的增殖、迁移和侵袭能力以及较低的摄碘能力。CAF具有更高的基础自噬水平;自噬抑制明显削弱了对PTC细胞的增殖、迁移和侵袭作用;而自噬激活促进了上述作用。荷瘤裸鼠动物实验证明自噬抑制后CAF对PTC移植瘤的促生长作用受到抑制。结论CAF可促进PTC细胞的增殖、迁移和侵袭,并降低其摄碘能力;CAF的自噬激活对PTC的恶性表型有促进作用。Objective To investigate the inpact of thyroid cancer-derived cancer-associated fibroblasts(CAF)autophagy on papillary thyroid cancer(PTC).Methods CAF and normal fibroblasts were isolated from cancerous and adjacent normal thyroid tissues from four PTC patients.Expressions of fibroblast activation protein(FAP)andα-smooth muscle actin in cells were assessed.Conditioned medium of CAF and normal fibroblasts were prepared and used to culture PTC cells.The effects of CAF and normal fibroblasts on survival,proliferation,migration,invasion and iodine uptake of PTC cells were evaluated through cell proliferation assay,cell scratch assay,cell invasion assay,and cell iodine uptake assay.The autophagy level of CAF was also evaluated.Autophagy inhibition and activation were used to regulate the autophagy of CAF,and then their effects on PTC cell proliferation,migration and invasion were further evaluated.The in vivo effect of CAF autophagy on PTC xenograft tumor growth was evaluated.Results CAF exhibited higher FAP expression and basal autophagy levels.PTC cells co-cultured with CAF-conditioned media showed enhanced proliferation,migration,invasion,and reduced iodine uptake.Autophagy inhibition reduced these effects,while autophagy activation further promoted them.In vivo,inhibiting CAF autophagy suppressed tumor growth.Conclusions CAF promotes PTC cell malignancy through autophagy activation,enhancing proliferation,migration,and invasion while reducing iodine uptake.

关 键 词：癌相关成纤维细胞 甲状腺乳头状癌 肿瘤微环境 自噬 

分 类 号：R736.1[医药卫生—肿瘤]