Open AccessFollistatin-like 1 deficiency impairs T cell development to promote lung metastasis of triple negative breast cancer
Author(s) -
Jie Ma,
Ying Yang,
Lulu Wang,
Xiaowei Jia,
Tao Lu,
Yiyan Zeng,
Li Liu,
Yan Gao
Publication year - 2021
Publication title -
aging
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.473
H-Index - 90
ISSN - 1945-4589
DOI - 10.18632/aging.202579
Subject(s) - follistatin , metastasis , triple negative breast cancer , breast cancer , medicine , lung , cancer research , lung cancer , cancer , breast cancer metastasis , oncology , cancer metastasis
Our study aims to detect the underlying mechanism of the suppressive effect of Follistatin-like 1 (FSTL1) on lung metastasis of triple negative breast cancer (TNBC). We found that FSTL1 had no effect on the proliferation and metastasis of 4T1 cells in vitro , while in the tumor-bearing Fstl1 heterozygous ( Fstl1 +/- ) mice, the number of anti-tumor T lymphocytes in the lung was significantly reduced with the increase in lung metastasis. Impaired development of T cells can cause dysfunction of adaptive immune system, which promotes cancer metastasis. Therefore the effect of FSTL1 on T cell development was further investigated. Lower population of T cells in periphery and decreased proliferation of CD4 - CD8 - double negative (DN) thymocytes and impairment development of T cells were found in Fstl1 +/- mice. Furthermore, high expression of FSTL1 in medullary thymus epithelial (mTEC) cells and decreased mRNA expression of inducible costimulator on activated T-cell ligand ( Icosl) in mTEC sh Fstl1 were detected. Combining other studies that the generation of ICOSL by mTEC cells promotes CD4 + single positive (SP) thymocytes to produce IL-2, which promotes T cell development. Our results indicate FSTL1 deficiency in mTEC cells impairs T cell development to promote the lung metastasis of TNBC.