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Impact of transforming growth factor beta 1 on normal and thyroid cancer side population cells

Lookup NU author(s): Dr Kamilla Mahkamova, Dr Joanna Elson, ISHA Karnik, Rachel Telfer-Sutherland, Seb Aspinall, Dr Annette Meeson



This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


© 2022, The Author(s). Purpose: To determine the impact of exogenous transforming growth factor beta 1 (TGF-β1) on side population (SP) cells isolated from normal, papillary thyroid cancer and anaplastic thyroid cancer cell lines and from human thyroid tissues. Methods: All cell populations were stained with Hoechst 33342 and analysed using dual wavelength flow cytometry to identify SP cells. This SP assay was used to assess the impact of TGF-β1 treatment and withdrawal of treatment on SP percentages. Semi-quantitative and quantitative PCR were used for molecular analysis of cells pre and post TGF-β1 treatment. Results: All cell lines expressed mRNA for both TGFB1 and its receptors, as well as showing variable expression of CDH1 and CDH2, with expressing of CDH1 being highest and CDH2 being lowest in the normal cell line. Exposure to exogenous TGF-β1 resulted in a reduction in mRNA expression of ABCG2 compared to controls which was significant between control and treated cancer cell lines. SP cells were isolated from primary human thyroid tissues, with numbers being significantly higher in papillary thyroid cancers. Exposure to TGF-β1 decreased the SP percentage in both thyroid cancer cell lines and completely abrogated these cells in the primary papillary thyroid cancer cultures. On withdrawal of TGF-β1 the SP phenotype was restored in the cancer cell lines and SP percentages increased to above that of untreated cells. Conclusions: TGF-β1 exposure transiently regulates thyroid cancer SP cells, leading to a reduction in SP percentages, while withdrawal of TGF-β1 results in restoration of the SP phenotype.

Publication metadata

Author(s): Latar NM, Mahkamova K, Elson J, Karnik I, Sutherland R, Aspinall S, Meeson A

Publication type: Article

Publication status: Published

Journal: Endocrine

Year: 2022

Volume: 76

Pages: 359-368

Print publication date: 01/05/2022

Online publication date: 03/02/2022

Acceptance date: 19/01/2022

Date deposited: 10/03/2022

ISSN (print): 1355-008X

ISSN (electronic): 1559-0100

Publisher: Springer Nature


DOI: 10.1007/s12020-022-02990-4

PubMed id: 35118633


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