Introduction: Adipocytes are known to be involved in epithelial-mesenchymal transition (EMT) associated with tumor cell invasion and metastasis in several cancers. However, the role of adipocytes in the EMT of breast cancer cells is poorly understood. The purpose of this study was to investigate the involvement of adipocytes in the EMT in breast cancer.

Methods: We investigated that co-culture with adipocytes induces morphological changes, proliferation activity, EMT markers expression, status of migration and invasion in MCF-7, MDA-MB-453, MDA-MB-435S, MDA-MB-231, and MDA-MB-468 cell lines. By tissue microarray (TMA) of 296 cases of human breast cancer, immunochemical staining for estrogen receptor (ER), progesterone (PR), HER2, Ki-67, N-cadherin, Twist1, HMGA2, TGFb, and S100A4 was conducted. We classified into fibrous stroma and adipose stroma (when adipose tissue is at least 50% of the entire tumor stroma) based on standard histological classification.

Results: After co-culture with adipocytes, MCF-7, MDA-MB-435S, and MDA-MB-231 cells exhibited elongated spindle-like morphology and increased proliferation; MDA-MB-435S and MDA-MB-231 cells also showed increased dispersion. In all tested breast cancer cells, adipocytes induced migration and invasion. The EMT-like phenotypic changes and increased cell migration and invasion were accompanied by the upregulation of matrix metallopeptidase 9 and TWIST1. Consistently, breast cancer tumors with the adipose stroma showed higher TWIST1 expression than those with the adipose stroma; however, no difference was observed in the levels of other EMT-related proteins.

Conclusion: Adipocytes enable breast cancer cells to acquire aggressive tumor biology by inducing EMT features, and breast cancer with adipose stroma expresses EMT markers as breast cancer with fibrous stroma.

Citation Format: Lee YuKyung, Kim Eun-Sol, Koo Ja Seung. Crosstalk between adipocytes and breast cancer promotes epithelial-mesenchymal transition. [abstract]. In: Proceedings of the AACR Special Conference on Translational Control of Cancer: A New Frontier in Cancer Biology and Therapy; 2016 Oct 27-30; San Francisco, CA. Philadelphia (PA): AACR; Cancer Res 2017;77(6 Suppl):Abstract nr A41.