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

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

Abstract

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Breast Neoplasms
  • Cell Culture Techniques
  • Cell Line, Tumor
  • Cell Shape*
  • Cluster Analysis
  • Collagen Type I / physiology
  • Female
  • Gene Expression Profiling
  • Gene Expression*
  • Humans
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Oligonucleotide Array Sequence Analysis

Substances

  • Collagen Type I
  • MIRN429 microRNA, human
  • MicroRNAs