Research Paper Volume 13, Issue 5 pp 7211—7227
Follistatin-like 1 deficiency impairs T cell development to promote lung metastasis of triple negative breast cancer
- 1 Beijing Key Laboratory of Cancer Invasion and Metastasis Research, Department of Human Anatomy, School of Basic Medical Sciences, Capital Medical University, Beijing, China
- 2 Department of Experimental Center for Basic Medical Teaching, School of Basic Medical Sciences, Capital Medical University, Beijing, China
Received: July 29, 2020 Accepted: December 19, 2020 Published: February 26, 2021
https://doi.org/10.18632/aging.202579How to Cite
Copyright: © 2021 Ma et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Abstract
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 mTECsh 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.
Abbreviations
FSTL1: Follistatin-like 1; TNBC: triple negative breast cancer; Th: T helper; DN: double negative; DP: double positive; CD4+ SP: CD4+ single positive; CD8+ SP: CD8+ single positive; mTECs: thymus medullary epithelial cells; ICOSL: inducible costimulator on activated T-cell ligand; IL: interleukin.