Side population cells in anaplastic thyroid cancer and normal thyroid

Exp Cell Res. 2019 Jan 1;374(1):104-113. doi: 10.1016/j.yexcr.2018.11.012. Epub 2018 Nov 19.

Abstract

Comparison of studies of cells derived from normal and pathological tissues of the same organ can be fraught with difficulties, particular with cancer where a number of different diseases are considered cancer within the same tissue. In the thyroid, there are 4 main types of cancer, three of which arise from follicular epithelial cells; papillary and follicular which are classified as differentiated, and anaplastic which is classified as undifferentiated. One assay that can be utilised for isolation of cancer stem cells is the side population (SP) assay. However, SP studies have been limited in part due to lack of optimal isolation strategies and in the case of anaplastic thyroid cancer (ATC) are further compounded by lack of access to ATC tumors. We have used thyroid cell lines to determine the optimal conditions to isolate viable SP cells. We then compared SP cells and NSP cells (bulk tumour cells without the SP) of a normal thyroid cell line N-thy ori-3-1 and an anaplastic thyroid cancer cell line SW1736 and showed that both SP cell populations displayed higher levels of stem cell characteristics than the NSP. When we compared SP cells of the N-thy ori-3-1 and the SW1736, the SW1736 SP had a higher colony forming potential, expressed higher levels of stem cell markers and CXCR4 and where more migratory and invasive, invasiveness increasing in response to CXCL12. This is the first report showing functional differences between ATC SP and normal thyroid SP and could lead to the identification of new therapeutic targets to treat ATC.

Keywords: Anaplastic thyroid cancer; Cancer; Cancer biology; Cancer stem cells; Cell invasion; Cell migration; Side population; Thyroid; Thyroid cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Asymmetric Cell Division / drug effects
  • Benzimidazoles / metabolism
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism
  • Cell Line, Tumor
  • Cell Movement / drug effects
  • Chemokine CXCL12 / pharmacology
  • Coloring Agents / metabolism
  • Humans
  • Neoplasm Invasiveness
  • Neoplasm Proteins / genetics
  • Neoplasm Proteins / metabolism
  • Neoplastic Stem Cells / drug effects
  • Neoplastic Stem Cells / metabolism
  • Neoplastic Stem Cells / pathology
  • Phenotype
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Receptors, CXCR4 / genetics
  • Receptors, CXCR4 / metabolism
  • Side-Population Cells / drug effects
  • Side-Population Cells / metabolism
  • Side-Population Cells / pathology*
  • Thyroglobulin / metabolism
  • Thyroid Carcinoma, Anaplastic / genetics
  • Thyroid Carcinoma, Anaplastic / pathology*
  • Thyroid Gland / drug effects
  • Thyroid Gland / metabolism
  • Thyroid Gland / pathology*
  • Tumor Stem Cell Assay

Substances

  • Benzimidazoles
  • Biomarkers, Tumor
  • Chemokine CXCL12
  • Coloring Agents
  • Neoplasm Proteins
  • RNA, Messenger
  • Receptors, CXCR4
  • Thyroglobulin
  • bisbenzimide ethoxide trihydrochloride