OBJECTIVE

Adipocytes are the most abundant stromal partners in breast tissue. However, the crosstalk between breast cancer cells and adipocytes has been given less attention compared to cancer-associated fibroblasts. We try to explain whether cancer associate adipocytes (CAAs) in microenvironment can lead to metabolic remodeling of triple-negative breast cancer, promoted cancer proliferation, migration and the potential mechanism.

METHOD

A Transwell co-culture model in vitro and orthotopic mouse model of human breast tumor formation in vivo were used to study the crosstalk between adipocytes and breast cancer cells, and then using clinical breast cancer sample analysis to study the mechanism of glutamine reprograming.

RESULTS

We find that while cocultivated adipocytes with breast cancer cells, it exhibited enhanced oxygen consumption rate (OCR) and ATP, accompanied by increasing glucose and glutamine uptake. Interestingly, the metabolic way is significantly different between phenotype-specific breast cancer cells. Compared with non-triple-negative breast cancer cells, triple-negative breast cancer cells (MDA-MB-231, MDA-MB-468) are more dependent on glutamine. We show that cancer associate adipocytes (CAAs) promote growth of breast cancer cells through key enzymes such as GLUL/GLS/GDH and transporters such as SLC1A5/SLC38A1/SLC38A2 related to glutamine metabolism in vitro. Using cytokine antibody microarrays, IL-6/IL-8/ leptin/TIPM2 is secreted by CAAs and is required to enhance breast cancer cells malignancy in vitro. Consistently, the correlation of inflammatory cytokines and adipokines with prognosis is analyzed by the Kaplan-Meier plotter, the data suggest that inflammatory cytokines and adipokines is associated with glutamine metabolism in triple-negative breast cancer microenvironment.

CONCLUSIONS

These results suggest that adipocytes promote proliferation of triple-negative breast cancer via metabolism reprogramming potentially by inducing inflammatory cytokines and adipokines upregulation of cancer associate adipocytes (CAAs).

Citation Format: Yang Liu, Tingli Zhao, Zhengzheng Li, Lai Wang, Mei Yang, Shengtao Yuan, Li Sun. Glutamine metabolism reprogramming in adipocyte-tumor microenvironment promotes triple-negative breast cancer growth [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 387.