Papillary Thyroid Cancer Tumor Spheres Cultured by Passaging Without Sorting Exhibit Cancer Stemness

Anticancer Res. 2020 Jul;40(7):3801-3809. doi: 10.21873/anticanres.14369.

Abstract

Aim: Cancer stem-like cell (CSC) markers and the role of CSCs derived from papillary thyroid carcinoma (PTC) in pathogenesis are unclear. This study aimed to investigate CSC properties using tumor spheres from passaged PTC cells but without sorting CSCs.

Materials and methods: To identify the properties of CSCs derived from PTC, the expression of SRY-box transcription factor 2(SOX2), octamer-binding transcription factor 4 (OCT4), Nanog homeobox (NANOG), thyroglobulin (TG), thyroid-stimulating hormone receptor (TSHR), E-cadherin, YES-associated protein 1 (YAP1), and signal transducer and activator of transcription 3 (STAT3) was investigated in tumor spheres serially passaged without sorting CSCs.

Results: The cultured tumor spheres had cancer stemness; high expression of OCT4, SOX2, NANOG, and YAP1; low expression of E-cadherin; and varied expression of TG, TSHR, and STAT3. PTC tumor spheres transfected with small interfering RNA targeting YAP1 had fewer CSC properties than the non-transfected tumor spheres did.

Conclusion: Tumor spheres derived from PTC cells by passaging without sorting CSCs have more stem-like cell properties, and less differentiation potential. Thus, this simple and cost-effective method can be used for the enrichment of PTC stemness for employment in cell-based models, reducing the need for use of animal models.

Keywords: Thyroid cancer; papillary; tumor stem cells.

MeSH terms

  • Adaptor Proteins, Signal Transducing / biosynthesis
  • Adaptor Proteins, Signal Transducing / genetics
  • Antigens, CD / biosynthesis
  • Antigens, CD / genetics
  • Biomarkers, Tumor / biosynthesis
  • Biomarkers, Tumor / genetics
  • Cadherins / biosynthesis
  • Cadherins / genetics
  • Cell Line, Tumor
  • Cell Proliferation / physiology
  • Humans
  • Neoplastic Stem Cells / metabolism
  • Neoplastic Stem Cells / pathology*
  • Octamer Transcription Factor-3 / biosynthesis
  • Octamer Transcription Factor-3 / genetics
  • STAT3 Transcription Factor / biosynthesis
  • STAT3 Transcription Factor / genetics
  • Spheroids, Cellular
  • Thyroid Cancer, Papillary / genetics
  • Thyroid Cancer, Papillary / metabolism
  • Thyroid Cancer, Papillary / pathology*
  • Thyroid Neoplasms / genetics
  • Thyroid Neoplasms / metabolism
  • Thyroid Neoplasms / pathology*
  • Transcription Factors / biosynthesis
  • Transcription Factors / genetics
  • YAP-Signaling Proteins

Substances

  • Adaptor Proteins, Signal Transducing
  • Antigens, CD
  • Biomarkers, Tumor
  • CDH1 protein, human
  • Cadherins
  • Octamer Transcription Factor-3
  • POU5F1 protein, human
  • STAT3 Transcription Factor
  • STAT3 protein, human
  • Transcription Factors
  • YAP-Signaling Proteins
  • YAP1 protein, human