Research Paper Volume 12, Issue 16 pp 16172—16182
Leptin promotes bone metastasis of breast cancer by activating the SDF-1/CXCR4 axis
- 1 The Fifth Department of Chemotherapy, Affiliated Tumor Hospital of Guangxi Medical University, Nanning, China
- 2 Department of Trauma Orthopedic and Hand Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, China
- 3 Guangxi Key Laboratory of Regenerative Medicine, Guangxi Medical University, Nanning, China
Received: February 5, 2020 Accepted: June 9, 2020 Published: August 18, 2020
https://doi.org/10.18632/aging.103599How to Cite
Copyright © 2020 Duan et al. This is an open-access article distributed under the terms of the Creative Commons Attribution (CC BY) 3.0 License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Abstract
Obesity is associated with an increased risk of tumorigenesis, and increased leptin levels can promote tumor metastasis. However, the effects of leptin on bone metastasis in breast cancer are not fully understood. Here, we examined leptin receptor expression and bone metastasis in tissue samples from 96 breast cancer patients. In addition, we investigated the effects of leptin on the metastatic capacity of breast cancer cells in vitro using a transwell assays. The results indicated that higher leptin receptor levels in breast cancer cells are associated with increased incidence of bone metastasis in breast cancer patients. Additionally, leptin promoted migration and invasion of breast cancer cells. The SDF-1/CXCR4 axis activated by leptin also promoted bone metastasis of breast cancer. Finally, increased CXCR4 expression was accompanied by high leptin receptor expression in bone metastatic tissues from breast cancer patients. These results indicate that leptin induces bone metastasis of breast cancer by activating the SDF-1/CXCR4 axis.
Abbreviations
SDF-1: stromal cell derived factor-1; CXCR4: CXC Chemokine receptrs4; Ob-R: leptin receptor; Ob-Rb: leptin receptor b; Ob-Rt: leptin receptor t; ObRs: leptin receptors; GPCRs: G protein-coupled receptors; RPMI 1640: Roswell Park Memorial Institute 1640; FBS: fetal bovine serum; RNA: RibonucleicAcid; PCR: Polymerase Chain Reaction; h: Hour; (qRT)-PCR: quantitative real-time (qRT)-PCR; (RT)-PCR: Real-time (RT)-PCR; cDNA: complementary deoxyribonucleic acid; SDS-PAGE: Sodium dodecyl sulfate polyacrylamide gel electrophoresis; PVDF: Polyvinylidene Fluoride; ECL: Enhanced Chemiluminescence; SD: Standard deviation; TNM: Tumor Node Metastasis; IHC: Immunological Histological Chemistry; EMT: Epithelial-mesenchymal transition; C-X-C motif: Chemokine; AMD3100: Plerixafor.