Cancer-associated adipocytes: emerging supporters in breast cancer

Abstract

Breast cancer (BC) is a malignant breast tumor confronted with high invasion, metastasis and recurrence rate, and adipocytes are the largest components in breast tissue. The aberrant adipocytes, especially the BC-neighbored cancer-associated adipocytes (CAAs), are found in the invasive front of BC. CAAs present a vicious phenotype compared with mature mammary adipocytes and mediate the crosstalk network between adipocytes and BC cells. By releasing multiple adipokines such as leptin, adiponectin, interleukin (IL)-6, chemokine ligand 2 (CCL2) and chemokine ligand 5 (CCL5), CAAs play essential roles in favor of proliferation, angiogenesis, dissemination, invasion and metastasis of BC. This article reviews the recent existing CAAs studies on the functions and mechanisms of adipocytes in the development of BC, including adipokine regulating, metabolic reprogramming, extracellular matrix (ECM) remodeling, microRNAs (miRNAs) and immune cell adjusting. Besides, adipocyte secretome and cellular interactions are implicated in the intervention to BC therapy and autologous fat grafting of breast reconstruction. Therefore, the potential functions and mechanisms of CAAs are very important for unveiling BC oncogenesis and progress. Deciphering the complex network between CAAs and BC is critical for designing therapeutic strategies and achieving the maximum therapeutic effects of BC.

Cancer-Associated Adipocytes in Breast Cancer: Causes and Consequences

“…The modification of the adipocyte phenotype by cancer cells induces a strong effect in tumor cells and possibly in other cells of the TME. In vitro and in vivo experiments demonstrated that CAAs play essential roles in favoring the proliferation, angiogenesis, dissemination, invasion, and metastasis of BC (reviewed in [ 18 , 100 ]). The wide range of molecules and metabolites secreted by CAAs can mediate these effects directly or indirectly, through the induction of the tumor immunosuppressive microenvironment ( Figure 4 ).…”

Multi-factor Evaluation of Tumor-infiltrating Lymphocytes in Laryngeal Squamous Cell Carcinoma and its Prognostic Value

“…On the other hand, TILV considers the percentage of stroma to the overall tumor when calculating iTILs, hence TILV may be more illuminative than iTILs. Secondly, many studies have shown that the frontier of tumor invasion is the part that best represents the real-time immune status of tumors [36][37][38]. Finally, when iTILs alone are not enough to evaluate the local immune status of tumors, TILV, and fTILs may provide additional information.…”

Crown-Like Structures in Breast Adipose Tissue: Early Evidence and Current Issues in Breast Cancer

“…Future studies should examine heterogeneity in associations by host and tumor characteristics as well as in treatments received. Given the proposed mechanisms of CLS-B and clinical evidence that obesity affects the pharmacokinetics and effectiveness of some chemo- and hormonal therapies [ 96 , 97 , 98 , 99 , 100 , 101 , 102 , 103 ], these lesions may affect certain subgroups of breast cancer patients more than others [ 1 , 104 ]. Adipocyte–tumor crosstalk is an active area of preclinical research, with some studies in breast and other cancers showing that adipocytes can promote chemoresistance through various mechanisms [ 105 , 106 ].…”