Abstract
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.
Highlights
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
Our results suggest that F7 peptide and SP peptide can serve as a tool to detect CSCs or EMT derived cells
To track the EMT-derived cells both in vitro and in vivo, we transduced the reporter genes to the human tongue squamous carcinoma derived cell line-SAS using lentivirus, which were referred as SAS-EGFP-Fluc and SAS-E2-crimson-P2A::ttksr[39] cells, respectively
Summary
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. The in vitro data showed that the F7 and SP peptides were capable of detecting EMT derived cells with high vimentin and nucleolin expressions. The fluorescent signal derived from F7 and SP peptides were found in SAS cells that are known to express vimentin and nucleolin.
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