Thymic function affects breast cancer development and metastasis by regulating expression of thymus secretions PTMα and Tβ15b1

Dongling Shi; Yanmei Shui; Xie Xu; Kai He; Fengqing Yang; Jianli Gao

doi:10.1016/j.tranon.2020.100980

Thymic function affects breast cancer development and metastasis by regulating expression of thymus secretions PTMα and Tβ15b1

Transl Oncol. 2021 Jan;14(1):100980. doi: 10.1016/j.tranon.2020.100980. Epub 2020 Dec 11.

Authors

Dongling Shi¹, Yanmei Shui¹, Xie Xu², Kai He³, Fengqing Yang⁴, Jianli Gao⁵

Affiliations

¹ Academy of Traditional Chinese Medicine, Zhejiang Chinese Medical University, Hangzhou, Zhejiang 310053, China.
² College of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou, Zhejiang 310053, China.
³ The First Affiliated Hospital, Zhejiang University, Hangzhou, Zhejiang 310009, China.
⁴ School of Chemistry and Chemical Engineering, Chongqing University, Chongqing 401331, China. Electronic address: fengqingyang@cqu.edu.cn.
⁵ Academy of Traditional Chinese Medicine, Zhejiang Chinese Medical University, Hangzhou, Zhejiang 310053, China. Electronic address: jianligao@zcmu.edu.cn.

Abstract

Breast cancer is currently one of the most common malignant tumors in women. Our previous research found that thymic dysfunction has a certain relationship with the occurrence and development of breast cancer. In order to explore whether the functional status of thymus is related to the development and metastasis of breast cancer, we use BALB/c wild type mice (BALB wt), BALB/c nude mice (BALB nu), BALB wt mice implanted with 4T1 cells (wt 4T1), BALB nu with 4T1 (nu 4T1), D-galactose treatment wt 4T1 mice (D-Gal), Thymalfasin treatment wt 4T1 mice (Tα1), Cyclophosphamide treatment wt 4T1 mice (CTX), Doxorubicin treatment wt 4T1 mice (Dox) in the research. As a result, nu 4T1, D-Gal and DOX had earlier lung metastases. Gene chip results showed that PTMα and Tβ15b1 were the most up-regulated and down-regulated genes in thymosin-related genes, respectively. Overexpression or silencing of PTMα and Tβ15b1 genes did not affect the proliferation of 4T1 cells. PTMα gene silenced, cell migration and invasion ability enhanced, while PTMα gene overexpression, the cell invasion ability weaken. In vivo, PTMα gene overexpression promotes tumor growth and lung metastasis in the early stage, but has no significant effect in the later stage. Tβ15b1 overexpression also promotes tumor growth in the early stage, but suppresses in the later stage. Tβ15b1 gene silencing inhibits tumor lung metastasis. Thus, our findings demonstrated that thymic function affects breast cancer development and metastasis by regulating expression of thymus secretions PTMα and Tβ15b1. Our study provided new directions for breast cancer therapy.

Keywords: Breast cancer; PTMα and Tβ15b1; Thymosin; Tumor metastasis.