FSTL1调控乳腺癌细胞干细胞样特性并增强耐药性的机制研究

Mechanism research of FSTL1 regulates chemoresistance and maintains stemness in breast cancer cells

目的:探讨卵泡抑素样蛋白1(follistatin like 1,FSTL1)在乳腺癌中的表达对肿瘤干细胞样特性及化疗耐药性的影响。方法:应用RT-PCR和免疫组化(IHC)等多种生物学实验方法,从临床标本实验的角度探究FSTL1促进乳腺癌细胞干细胞和化疗耐药性的作用及可能与miR-137/FSTL1/整合素β3/Wnt/β-联蛋白信号通路的相关性。结果:FSTL1在三阴性乳腺癌(triple negative breast cancer,TNBC)组织及细胞系中的表达显著高于非TNBC组织及细胞系。耐药TNBC细胞系中FSTL1的表达亦显著高于其在母细胞系中的表达。研究证实FSTL1可促进乳腺癌干细胞表面标志物的表达上调,并促进肿瘤细胞集落形成和球体形成。FSTL1通过调控整合素β3表达进而活化Wnt/β-联蛋白信号通路发挥其生物学作用,而miR-137则可负性调控FSTL1的表达。结论:FSTL1能促进乳腺癌细胞干细胞样特性和化疗耐药性,乳腺癌细胞中存在miR-137/FSTL1/整合素β3/Wnt/β-联蛋白信号轴调节干细胞的功能和化疗耐药性。

Objective： To investigate the effect of FSTL1 expression in breast cancer on stem cell-like characteristics and chemotherapy resistance. Methods： RT-PCR and immunohistochemistry（ IHC） were used to investigate the role of FSTL1 in the promotion of breast cancer stem cells and chemotherapeutic resistance and possible miR-137/FSTL1 from the perspective of clinical specimens. Correlation of Integrin β3/Wnt/β-catenin signaling pathway.Results： The expression of TNBC in breast cancer tissues and cell lines was significantly higher than that of non-TNBC breast cancer tissues and cell lines. The expression of FSTL1 in the resistant TNBC cell line was also significantly higher than that in the parental cell line. Studies have confirmed that FSTL1 can promote the expression of breast cancer stem cell surface markers and promote tumor colony formation and sphere formation. FSTL1 regulates the expression of Integrin β3 and activates Wnt/β-catenin signaling pathway to exert its biological effects,while miR-137 can negatively regulate FSTL1 expression. Conclusion： FSTL1 can promote stem cell and chemoresistance in breast cancer cells. There are miR-137/FSTL1/Integrin β3/Wnt/β-catenin signaling axis in breast cancer cells,regulating stem cell function and chemoresistance.