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Adipocytes can induce epithelial-mesenchymal transition in breast cancer cells

 YuKyung Lee  ;  Woo Hee Jung  ;  Ja Seung Koo 
 Breast Cancer Research and Treatment, Vol.153(2) : 323-35, 2015 
Journal Title
 Breast Cancer Research and Treatment 
Issue Date
3T3-L1 Cells ; Adipocytes/metabolism* ; Adipocytes/pathology ; Animals ; Biomarkers ; Breast Neoplasms/genetics ; Breast Neoplasms/metabolism* ; Breast Neoplasms/pathology* ; Cell Line, Tumor ; Cell Movement ; Cell Proliferation ; Coculture Techniques ; Epithelial-Mesenchymal Transition*/genetics ; Female ; Gene Expression ; Humans ; Immunohistochemistry/methods ; Mice ; Neoplasm Grading ; Neoplasm Staging ; Phenotype ; Stromal Cells/metabolism ; Stromal Cells/pathology
Adipocytes ; Breast cancer ; Epithelial-mesenchymal transition ; Stroma
Adipocytes are known to be involved in epithelial-mesenchymal transition (EMT) 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. Breast cancer cell lines MCF-7, MDA-MB-453, MDA-MB-435S, MDA-MB-231, and MDA-MB-468 were co-cultured with adipocytes and analyzed for morphological changes, proliferation activity, EMT markers, migration, and invasion. In addition, 296 human breast cancer specimens were classified according to the presence of the fibrous or adipose stroma and analyzed by immunohistochemistry for the expression of estrogen and progesterone receptors, human epidermal growth factor receptor 2, antigen Ki-67, N-cadherin, Twist-related protein 1 (TWIST1), high-mobility group AT-hook 2, TGFβ, and S100 calcium-binding protein A4 using tissue microarray. 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. Adipocytes stimulate breast cancer cells to acquire aggressive tumor phenotype by inducing EMT-associated traits, and breast cancer with the adipose stroma expresses EMT markers as breast cancer with the fibrous stroma.
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1. College of Medicine (의과대학) > Dept. of Pathology (병리학교실) > 1. Journal Papers
Yonsei Authors
Koo, Ja Seung(구자승) ORCID logo https://orcid.org/0000-0003-4546-4709
Lee, Yu Kyung(이유경)
Jung, Woo Hee(정우희)
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