Galectin-1 Influences Breast Cancer Cell Adhesion to E-selectin Via Ligand Intermediaries.
Galectin-1 Influences Breast Cancer Cell Adhesion to E-selectin Via Ligand Intermediaries.
复制标题
Galectin-1 通过配体中间体影响乳腺癌细胞对 E-选择素的粘附。
DOI：
10.1007/s12195-017-0512-9
复制
发表时间：
2018
影响因子：
2.8
通讯作者：
Burdick,MonicaM
中科院分区：
文献类型：
--
作者：
Reynolds,NathanM;Mohammadalipour,Amina;Hall,ClaireR;AsghariAdib,Ali;Farnoud,AmirM;Burdick,MonicaM
血液转移过程中其他组织的侵袭部分需要癌细胞通过特异性流体剪切依赖性受体-配体相互作用粘附到血管内皮上。本研究探讨了粘附是由内皮细胞E-选择素和半乳糖凝集素-1（Galectin-1，Gal-1）之间共享的配体介导的假说，两者在炎症和癌症中均被上调。方法采用流动室粘附和动态生物化学组织分析（DBTA）测定来评估Gal-1是否在动态流动条件下调节乳腺癌细胞和组织的E-选择素粘附相互作用，同时采用免疫细胞化学，免疫组化，蛋白质印迹，和荧光各向异性被用来研究静态conditions.ResultsDynamic粘附测定下的分子相互作用揭示了Gal-1hFc处理的乳腺癌细胞和组织和E-选择素包被的珠之间的剪切依赖性的结合相互作用，导致~ 300%的结合增加的珠相比，阴性对照。免疫细胞和免疫组织化学分析表明，Gal-1和E-选择素的荧光信号共定位在细胞和组织上，在每一个试验约75%。乳腺癌细胞裂解物中Mac-2BP的免疫沉淀和Western印迹显示，Gal-1和E-选择素共享Mac-2BP作为配体，而荧光各向异性和循环肿瘤细胞模型系统表现出Gal-1和E-选择素之间的竞争性或拮抗性结合共享配体，包括Mac-2BP。此外，Mac-2BP功能阻滞抑制Gal-1对E-selectin binding.ConclusionsIn总结，这项调查揭示了剪切依赖性E-选择素和Gal-1之间的相互作用，这可能是由于中介的一个类似的或共享的配体（S），包括Mac-2BP，这可能提供了一个合理的基础上开发新的诊断或治疗乳腺癌。
IntroductionInvasion of other tissues during bloodborne metastasis in part requires adhesion of cancer cells to vascular endothelium by specific fluid shear-dependent receptor–ligand interactions. This study investigates the hypothesis that the adhesion is mediated by ligands shared between endothelial E-selectin and Galectin-1 (Gal-1), both of which are upregulated during inflammation and cancer.MethodsFlow chamber adhesion and dynamic biochemical tissue analysis (DBTA) assays were used to evaluate whether Gal-1 modulates E-selectin adhesive interactions of breast cancer cells and tissues under dynamic flow conditions, while immunocytochemistry, immunohistochemistry, western blotting, and fluorescence anisotropy were used to study molecular interactions under static conditions.ResultsDynamic adhesion assays revealed a shear-dependent binding interaction between Gal-1hFc treated breast cancer cells and tissues and E-selectin-coated beads, causing ~ 300% binding increase of the beads compared to negative controls. Immunocyto- and immunohistochemical analyses showed that Gal-1 and E-selectin fluorescent signals colocalized on cells and tissues at ~ 75% for each assay. Immunoprecipitation and Western blotting of Mac-2BP from breast cancer cell lysates revealed that Gal-1 and E-selectin share Mac-2BP as a ligand, while fluorescence anisotropy and circulating tumor cell model systems exhibited competitive or antagonistic binding between Gal-1 and E-selectin for shared ligands, including Mac-2BP. Furthermore, Mac-2BP functional blockade inhibited the effects of Gal-1 on E-selectin binding.ConclusionsIn summary, this investigation reveals a shear-dependent interaction between E-selectin and Gal-1 that may be due to intermediation by a similar or shared ligand(s), including Mac-2BP, which may provide a rational basis for development of novel diagnostics or therapeutics for breast cancer.