Adipose-derived stem cells enhance human breast cancer growth and cancer stem cell-like properties through adipsin

Abstract

Tumor microenvironment plays a key role for tumor development and progression. Although adipose tissue is a predominant component of stroma in mammary tissues and secretes various cytokines, chemokines and growth factors, roles of adipocytes in breast cancers remain to be elucidated. In this study, we found that adipsin, an adipokine secreted from mammary adipose tissues, enhanced proliferation and cancer stem cell (CSC)-like properties of human breast cancer patient-derived xenograft (PDX) cells. Adipsin was predominantly expressed in both adipose tissues of the surgical specimens of breast cancer patients and adipose-derived stem cells (ADSCs) isolated from them, and its expression level was significantly higher in obese patients. ADSCs significantly enhanced the sphere-forming ability of breast cancer PDX cells derived from both estrogen receptor-positive and -negative breast cancer PDX cells. Suppression of adipsin-mediated signaling by a specific inhibitor or adipsin knockdown in ADSCs significantly decreased the sphere-forming ability and the expression of CSC markers in co-cultured breast cancer PDX cells. Growth of breast cancer PDX tumors was significantly enhanced by co-transplantation with ADSCs in vivo, and it was weakened when co-transplanted with the adipsin knocked-down ADSCs. These results suggest that adipsin is an important adipokine secreted from mammary adipose tissue that functions as a component of tumor microenvironment and a CSC niche in breast cancers.

MicroRNA‐93 targets WASF3 and functions as a metastasis suppressor in breast cancer

“…To analyze the expression levels of mRNAs, RNA samples were reverse transcribed using a High Capacity cDNA Reverse Transcription Kit (Life Technologies). Semiquantitative PCR was undertaken as described previously 23 . The sequences of primers used are presented in Table .…”

Prognostic Significance of the Tumor-Stromal Ratio in Invasive Breast Cancer and a Proposal of a New Ts-TNM Staging System

“…Recently, accumulating evidence suggests that tumor progression and metastasis are not only affected by biological behaviors of cancer cells but also by tumor microenvironments (TMEs), which are defined as the bidirectional interactions between tumor cells, stromal cells, and cellular elements [10,11]. Tumor stroma, as an important component of TME, promotes tumor progression through production of various nutrition, growth factors, chemokines, and cytokines [12][13][14]. As a result, the tumor-stromal ratio (TSR), a new parameter that represents the proportion of tumor-associated stroma, was introduced to the field of cancer research [15].…”

Exosomes From Adipose-Derived Stem Cells: The Emerging Roles and Applications in Tissue Regeneration of Plastic and Cosmetic Surgery

“…Studies have demonstrated the survival rate, growth, and invasiveness of tumors after interacting with ASCs, which are CAAs components. By excreting a variety of bioactive factors including visfatin, adipsin, CCL5, IGF, HGF, VEGF, IL-8, and TGF-β, ASCs can exert biological influences on proliferation, epithelial-mesenchymal transition, and metastasis ( Huang et al, 2019 ; Goto et al, 2019 ). ASCs could differentiate into cancer-associated fibroblasts in breast cancer environment, especially with a more pronounced effect on obese patients ( Cho et al, 2012 ; Ecker et al, 2019 ).…”