转化生长因子β1在血小板促进甲状腺未分化癌侵袭迁移中的作用

Role and Mechanism of TGFβ1 in Platelet Promoting Invasion and Migration of Anaplastic Thyroid Carcinoma Cells

目的探索肿瘤患者血小板(platelet,PLT)是否通过分泌转化生长因子β1(transforming growth factorβ1,TGFβ1)参与调控甲状腺未分化癌(anaplastic thyroid carcinoma,ATC)的转移。方法通过ELISA和Real-time PCR实验测定ATC细胞上清TGFβ1蛋白和mRNA表达情况;通过Transwell迁移实验、划痕实验和Western Blot方法探究TGFβ1对ATC细胞迁移及侵袭能力的影响及其作用机制。结果PLT与ATC细胞共培养上清液中TGFβ1蛋白水平显著上调(P<0.001)而mRNA水平不变;PLT或rhTGFβ1可使穿过小室的ATC细胞显著增加(P<0.001),提示PLT或rhTGFβ1能显著增强ATC细胞的迁移能力(P<0.001);划痕实验也证实rhTGFβ1可显著增强ATC细胞的迁移能力(P<0.001)。结论PLT可通过分泌TGFβ1诱导ATC细胞EMT进程最终增强ATC细胞迁移和侵袭能力,表明TGFβ1可能成为ATC患者靶向治疗的潜在靶标。

Objective This study aims to explore whether platelet(PLT)is involved in regulating the progression of anaplastic thyroid carcinoma(ATC)by secreting transforming growth factorβ1(TGFβ1).Methods The levels of TGFβ1 protein and mRNA in the supernatant of ATC cells were detected by ELISA and Real-time PCR,respectively.Transwell,scratch wound test and Western Blot were used to analyze the effects of TGFβ1 on the invasive and migratory abilities of ATC cell lines and its mechanism.Results In the co-culture supernatant of PLT and ATC cells,the protein level of TGFβ1 was significantly up-regulated,but the mRNA level was unchanged.PLT or rhTGF-β1 significantly increased the number of ATC cells crossing the chamber(P<0.001),suggesting that PLT or rhTGF-β1 could significantly enhance the migration ability of ATC cells.Scratch wound assay also confirmed that rhTGF-β1 could significantly enhance the migration ability of ATC cells.Conclusion PLT can significantly promote the development of EMT in ATC cells by secreting TGFβ1,and then promote the invasion and migration of ATC cells,suggesting that TGFβ1 may be a potential target of ATC molecular targeted therapy.