Detection of cancer stem cells by EMT-specific biomarker-based peptide ligands

Sci Rep. 2021 Nov 17;11(1):22430. doi: 10.1038/s41598-021-01138-0.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biomarkers, Tumor / metabolism
  • Carcinoma, Squamous Cell / metabolism*
  • Carcinoma, Squamous Cell / pathology
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Dimethyl Sulfoxide / administration & dosage
  • Epithelial-Mesenchymal Transition* / drug effects
  • Epithelial-Mesenchymal Transition* / radiation effects
  • Humans
  • Ligands
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Neoplastic Stem Cells / metabolism*
  • Peptides / metabolism*
  • Quinazolines / administration & dosage
  • Spheroids, Cellular
  • Tongue Neoplasms / metabolism*
  • Tongue Neoplasms / pathology
  • Tumor Burden / drug effects
  • Tumor Burden / radiation effects
  • Vimentin / metabolism*
  • Xenograft Model Antitumor Assays

Substances

  • Biomarkers, Tumor
  • Ligands
  • Peptides
  • Quinazolines
  • UNC0642
  • VIM protein, human
  • Vimentin
  • Dimethyl Sulfoxide