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Regulatory T cells inhibit FoxP3 to increase the population of tumor initiating cells in hepatocellular carcinoma.
Liu, Chang; Tu, Yi-Jun; Cai, Hong-Yang; Pan, Yan-Yan; Wu, Yuan-Yuan; Zhang, Li.
Afiliación
  • Liu C; Central Hospital of Dalian University of Technology, No. 826, Southwest Road, Dalian, 116033, China.
  • Tu YJ; Central Hospital of Dalian University of Technology, No. 826, Southwest Road, Dalian, 116033, China.
  • Cai HY; Central Hospital of Dalian University of Technology, No. 826, Southwest Road, Dalian, 116033, China.
  • Pan YY; Central Hospital of Dalian University of Technology, No. 826, Southwest Road, Dalian, 116033, China.
  • Wu YY; Central Hospital of Dalian University of Technology, No. 826, Southwest Road, Dalian, 116033, China.
  • Zhang L; Central Hospital of Dalian University of Technology, No. 826, Southwest Road, Dalian, 116033, China. tyouri19652004@hotmail.com.
J Cancer Res Clin Oncol ; 150(7): 373, 2024 Jul 29.
Article en En | MEDLINE | ID: mdl-39073490
ABSTRACT

PURPOSE:

Tumor initiating cells (TICs) or cancer stem cells (CSCs) are considered to be the main culprit of hepatocellular carcinoma (HCC) initiation and progression, nevertheless the mechanism by which tumor microenvironment maintains the HCC 'stemness' is not fully understood. This study aims to investigate the effect of regulatory T cells (Tregs) on the TICs characteristics of HCC.

METHODS:

Immunocytochemistry, flow cytometry, real-time PCR, western blot, in vitro sphere-formation, and in vivo tumorigenesis assay were used to detect HCC 'stemness'. Additionally, after forced expression or inhibition of FoxP3, ß-catenin expression and HCC 'stemness' were investigated.

RESULTS:

Tregs enhanced the 'stemness' of HCC cells by upregulating TIC-related markers CD133, Oct3/4, Sox2, c-Myc, Klf4, Nanog, CD13, EpCAM, and inducting epithelial to mesenchymal transition (EMT), increasing TICs ratio, as well as promoting tumorigenic ability. Moreover, ß-catenin and c-Myc were upregulated in HCC cells after co-cultured with Tregs. HCC 'stemness' was inhibited after treatment with Wnt/ß-catenin pathway inhibitor. Furthermore, forced expression of FoxP3 resulted in increased GSK3ß, decreased ß-catenin and TIC ratio in HCC. In contrast, FoxP3 interference reduced GSK3ß, enhanced ß-catenin and TIC ratio of HCC.

CONCLUSION:

This study, for the first time, demonstrated that Tregs increased the population of TICs in HCC by inhibiting FoxP3 as well as promoting ß-catenin expression.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Células Madre Neoplásicas / Linfocitos T Reguladores / Carcinoma Hepatocelular / Factores de Transcripción Forkhead / Factor 4 Similar a Kruppel / Neoplasias Hepáticas Límite: Animals / Humans Idioma: En Revista: J Cancer Res Clin Oncol Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Alemania
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Células Madre Neoplásicas / Linfocitos T Reguladores / Carcinoma Hepatocelular / Factores de Transcripción Forkhead / Factor 4 Similar a Kruppel / Neoplasias Hepáticas Límite: Animals / Humans Idioma: En Revista: J Cancer Res Clin Oncol Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Alemania