Bone Marrow Adipocytes, Adipocytokines, and Breast Cancer Cells: Novel Implications in Bone Metastasis of Breast Cancer.

Chang Liu,Xijie Yu,Qian Zhao

doi:10.3389/fonc.2020.561595

Abstract

Accumulating discoveries highlight the importance of interaction between marrow stromal cells and cancer cells for bone metastasis. Bone is the most common metastatic site of breast cancer and bone marrow adipocytes (BMAs) are the most abundant component of the bone marrow microenvironment. BMAs are unique in their origin and location, and recently they are found to serve as an endocrine organ that secretes adipokines, cytokines, chemokines, and growth factors. It is reasonable to speculate that BMAs contribute to the modification of bone metastatic microenvironment and affecting metastatic breast cancer cells in the bone marrow. Indeed, BMAs may participate in bone metastasis of breast cancer through regulation of recruitment, invasion, survival, colonization, proliferation, angiogenesis, and immune modulation by their production of various adipocytokines. In this review, we provide an overview of research progress, focusing on adipocytokines secreted by BMAs and their potential roles for bone metastasis of breast cancer, and investigating the mechanisms mediating the interaction between BMAs and metastatic breast cancer cells. Based on current findings, BMAs may function as a pivotal modulator of bone metastasis of breast cancer, therefore targeting BMAs combined with conventional treatment programs might present a promising therapeutic option.

Highlights

Breast cancer is the most common cancer among women and it leads to the second most tumorrelated deaths in women worldwide [1, 2]
We provide an overview of research progress, focusing on secreted adipocytokines by bone marrow adipocytes (BMAs) and their potential roles for bone metastasis of breast cancer, and investigating the mechanisms mediating the interaction between BMAs and metastatic breast cancer cells
IL-6 regulates breast cancer stem cell (CSC)-associated OCT4 gene expression through the JAK/STAT3 signal pathway in non-stem cancer cells (NSCCs). Inhibiting this pathway by treatment with anti-IL-6 antibody effectively prevents OCT4 gene expression. These results suggest that the IL-6/JAK/STAT3 signal pathway plays an important role in the conversion of NSCCs into CSCs through regulating OCT4 gene expression [82]

Summary

Introduction

Breast cancer is the most common cancer among women and it leads to the second most tumorrelated deaths in women worldwide [1, 2]. Many efforts have been made to uncover the functions of the bone marrow microenvironment and research the role of each cell type in tumor growth and metastasis [8]. Increasing evidence has highlighted the important role of adipocytokines as an active player involved in breast cancer progression and metastasis by remodeling extracellular matrix (ECM), modulating immune responses, influencing epithelial-mesenchymal transition (EMT), inducing cancer stem cell-like traits, increasing cancer cells proliferation and growth, and regulating angiogenesis [27].

Results

Conclusion