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Oncol Rep. 2012 Jul;28(1):117-126. doi: 10.3892/or.2012.1764. Epub 2012 Apr 19.

The microRNA expression associated with morphogenesis of breast cancer cells in three-dimensional organotypic culture.

Author information

Department of Medicine, Tulane University School of Medicine, 1430 Tulane Avenue, New Orleans, LA 70112, USA.
Key Laboratory of Cancer Proteomics of Chinese Ministry of Health, Xiangya Hospital, Central South University, Hunan 41008.
Department of Pathology, Tulane University School of Medicine, 1430 Tulane Avenue, New Orleans, LA 70112, USA.
Department of Obstetrics and Gynecology, Institute of Obstetrics and Gynecology, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, P.R. China.
Contributed equally


Three-dimensional organotypic culture using reconstituted basement membrane matrix Matrigel (rBM 3-D) is an indispensable tool to characterize morphogenesis of mammary epithelial cells and to elucidate the tumor-modulating actions of extracellular matrix (ECM). microRNAs (miRNAs) are a novel class of oncogenes and tumor suppressors. The majority of our current knowledge of miRNA expression and function in cancer cells is derived from monolayer 2-D culture on plastic substratum, which lacks consideration of the influence of ECM-mediated morphogenesis on miRNAs. In the present study, we compared the expression of miRNAs in rBM 3-D and 2-D cultures of the non-invasive MCF-7 and the invasive MDA-MB231 cells. Our findings revealed a profound difference in miRNA profiles between 2-D and rBM 3-D cultures within each cell type. Moreover, rBM 3-D culture exhibited greater discrimination in miRNA profiles between MCF-7 and MDA-MB231 cells than 2-D culture. The disparate miRNA profiles correlated with distinct mass morphogenesis of MCF-7 and invasive stellate morphogenesis of MDA-MB231 cells in rBM 3-D culture. Supplementation of the tumor promoting type I collagen in rBM 3-D culture substantially altered the miRNA signature of mass morphologenesis of MCF-7 cells in rBM 3-D culture. Overexpression of the differentially expressed miR-200 family member miR429 in MDA-MB231 cells attenuated their invasive stellate morphogenesis in rBM 3-D culture. In summary, we provide the first miRNA signatures of morphogenesis of human breast cancer cells in rBM 3-D culture and warrant further utilization of rBM 3-D culture in investigation of miRNAs in breast cancer.

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