Department of Biomedical Imaging and Radiological Sciences, National Yang Ming Chiao Tung University, Taipei, 112, Taiwan.
Molecular and Genetic Imaging Core/Taiwan Mouse Clinic, National Comprehensive Mouse Phenotyping and Drug Testing Center, Taipei, 112, Taiwan.
Sci Rep. 2021 Nov 17;11(1):22430. doi: 10.1038/s41598-021-01138-0.
The occurrence of epithelial-mesenchymal transition (EMT) within tumors, which enables invasion and metastasis, is linked to cancer stem cells (CSCs) with drug and radiation resistance. We used two specific peptides, F7 and SP peptides, to detect EMT derived cells or CSCs. Human tongue squamous carcinoma cell line-SAS transfected with reporter genes was generated and followed by spheroid culture. A small molecule inhibitor-Unc0642 and low-dose ionizing radiation (IR) were used for induction of EMT. Confocal microscopic imaging and fluorescence-activated cell sorting analysis were performed to evaluate the binding ability and specificity of peptides. A SAS xenograft mouse model with EMT induction was established for assessing the binding affinity of peptides. The results showed that F7 and SP peptides not only specifically penetrated into cytoplasm of SAS cells but also bound to EMT derived cells and CSCs with high nucleolin and vimentin expression. In addition, the expression of CSC marker and the binding of peptides were increased in tumors isolated from Unc0642/IR-treated groups. Our study demonstrates the potential of these peptides for detecting EMT derived cells or CSCs and might provide an alternative isolation method for these subpopulations within the tumor in the future.
肿瘤中上皮-间充质转化(EMT)的发生,使其具有侵袭和转移的能力,与具有耐药性的癌症干细胞(CSCs)有关。我们使用两种特定的肽,F7 和 SP 肽,来检测 EMT 衍生细胞或 CSCs。构建了转染报告基因的人舌鳞癌细胞系-SAS,并进行球体培养。小分子抑制剂-Unc0642 和低剂量电离辐射(IR)用于诱导 EMT。通过共聚焦显微镜成像和荧光激活细胞分选分析来评估肽的结合能力和特异性。建立了具有 EMT 诱导的 SAS 异种移植小鼠模型,以评估肽的结合亲和力。结果表明,F7 和 SP 肽不仅特异性地穿透 SAS 细胞的细胞质,而且还与具有高核仁素和波形蛋白表达的 EMT 衍生细胞和 CSCs 结合。此外,从 Unc0642/IR 处理组分离的肿瘤中,CSC 标志物的表达和肽的结合增加。我们的研究表明这些肽具有检测 EMT 衍生细胞或 CSCs 的潜力,并且将来可能为肿瘤内这些亚群提供一种替代的分离方法。