Adipocytes can induce epithelial-mesenchymal transition in breast cancer cells

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• 作者：YuKyung Lee ; Woo Hee Jung ; Ja Seung Koo
• 关键词：Adipocytes ; Breast cancer ; Epithelial ; mesenchymal transition ; Stroma
• 刊名：Breast Cancer Research and Treatment
• 出版年：2015
• 出版时间：September 2015
• 年：2015
• 卷：153
• 期：2
• 页码：323-335
• 全文大小：10,525 KB
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• 作者单位：YuKyung Lee (1)
  Woo Hee Jung (1)
  Ja Seung Koo (1)
  
  1. Department of Pathology, Severance Hospital, Yonsei University College of Medicine, 50 Yonsei-ro, Seodaemun-gu, Seoul, 120-752, South Korea
  
• 刊物类别：Medicine
• 刊物主题：Medicine & Public Health
  Oncology
  
• 出版者：Springer Netherlands
• ISSN：1573-7217

文摘

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. Keywords Adipocytes Breast cancer Epithelial-mesenchymal transition Stroma