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

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.

Overexpression of centromere protein K (CENPK) gene in Differentiated Thyroid Carcinoma promote cell Proliferation and Migration

“…Yes-associated protein (YAP1) is a direct effector in the downstream Hippo pathway, which regulates numerous protein targets for regulating gene level, cell contact, proliferation, or apoptosis [ 32 ]. Recent evidence indicated that PTC tumor spheres transfected with siRNA targeting YAP1 had less differentiation potential [ 33 ]. However, whether CENPK–YAP1–EMT axis is involved in the tumorigenesis of DTC needs further exploration.…”

Progression and dormancy in metastatic thyroid cancer: concepts and clinical implications

“…polarized epithelial cuboidal thyroid follicular cells) to a fibroblastoid morphology that enables invasive capacity [21,22]. Cancer stem cells (CSC's) are a slowly dividing, relatively treatment-resistant population of cells that exhibit plasticity in response to therapeutic or environmental challenges and express genes and surface markers [21,[23][24][25]. Cells that have undergone EMT and CSCs are critical in all components of the metastatic cascade and demonstrate the considerable "plasticity" of cancer cells.…”