A breast cancer cell microarray (CMA) as a rapid method to characterize candidate biomarkers

Cancer Biol Ther. 2014;15(12):1593-9. doi: 10.4161/15384047.2014.961886.

Abstract

Tissue microarrays (TMAs) have become an invaluable tool in cancer research to evaluate expression and subcellular localization of proteins in cells and tissues. As the catalogs of candidate biomarkers and therapeutic targets become more extensive, there is a need to characterize and validate these targets and biomarkers in cell lines as a primary biological system in research laboratories. Thus, cell microarrays (CMAs) are useful as a high-throughput screening tool. Here, we constructed a CMA containing 32 publicly available immortalized breast cell lines with the goal of creating a method to rapidly screen for antigens of interest in breast cancer research in a relatively easy, rapid and cost-effective manner. As proof of concept, we performed immunocytochemical staining of the HER2 receptor, as the status of this protein is relevant to breast cancer and has previously been reported for these cell lines. We observed a complete concordance of our staining with the published status of HER2 in these cell lines. In addition, we examined the expression of CD44, epithelial markers EpCAM and E-cadherin and tyrosine phosphoproteins. The labeling of these proteins correlates with the known biology of the cell lines. Our results demonstrate the utility of our method to screen for potential biomarkers and therapeutic targets in breast cancer and we suggest that CMAs be used as a general approach in breast cancer research.

Keywords: CD44; CMA, cell microarray; E-cadherin; ER, estrogen receptor; EpCAM; HER2; ICC, immunocytochemical staining; IHC, immunohistochemical staining; PR, progesterone receptor; TMA, tissue microarray; TNBC, triple negative breast cancer; biomarker; breast cancer; cell microarray; immunocytochemical staining; phosphorylation.

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

  • Antigens, Neoplasm / metabolism
  • Biomarkers, Tumor / metabolism*
  • Breast Neoplasms / metabolism*
  • Cadherins / metabolism
  • Cell Adhesion Molecules / metabolism
  • Cell Line, Tumor
  • Epithelial Cell Adhesion Molecule
  • Female
  • Humans
  • Hyaluronan Receptors / metabolism
  • Immunohistochemistry
  • Phosphoproteins / metabolism
  • Receptor, ErbB-2 / genetics
  • Tissue Array Analysis* / methods

Substances

  • Antigens, Neoplasm
  • Biomarkers, Tumor
  • Cadherins
  • Cell Adhesion Molecules
  • Epithelial Cell Adhesion Molecule
  • Hyaluronan Receptors
  • Phosphoproteins
  • Receptor, ErbB-2