Using Microarrays to Interrogate Microenvironmental Impact on Cellular Phenotypes in Cancer

Rebecca Smith, Kaylyn Devlin, David Kilburn, Sean Gross, Damir Sudar, Elmar Bucher, Michel Nederlof, Mark Dane, Joe W. Gray, Laura Heiser, James Korkola

Research output: Contribution to journalArticle

Abstract

Understanding the impact of the microenvironment on the phenotype of cells is a difficult problem due to the complex mixture of both soluble growth factors and matrix-associated proteins in the microenvironment in vivo. Furthermore, readily available reagents for the modeling of microenvironments in vitro typically utilize complex mixtures of proteins that are incompletely defined and suffer from batch to batch variability. The microenvironment microarray (MEMA) platform allows for the assessment of thousands of simple combinations of microenvironment proteins for their impact on cellular phenotypes in a single assay. The MEMAs are prepared in well plates, which allows the addition of individual ligands to separate wells containing arrayed extracellular matrix (ECM) proteins. The combination of the soluble ligand with each printed ECM forms a unique combination. A typical MEMA assay contains greater than 2,500 unique combinatorial microenvironments that cells are exposed to in a single assay. As a test case, the breast cancer cell line MCF7 was plated on the MEMA platform. Analysis of this assay identified factors that both enhance and inhibit the growth and proliferation of these cells. The MEMA platform is highly flexible and can be extended for use with other biological questions beyond cancer research.

Original languageEnglish (US)
JournalJournal of visualized experiments : JoVE
Issue number147
DOIs
StatePublished - May 21 2019

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Microarrays
Assays
Proteins
Complex Mixtures
Phenotype
Ligands
Cellular Microenvironment
Neoplasms
Extracellular Matrix Proteins
Extracellular Matrix
Intercellular Signaling Peptides and Proteins
Cell Proliferation
Breast Neoplasms
Cell Line
Cells
Growth
Research

ASJC Scopus subject areas

  • Neuroscience(all)
  • Chemical Engineering(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

Cite this

Using Microarrays to Interrogate Microenvironmental Impact on Cellular Phenotypes in Cancer. / Smith, Rebecca; Devlin, Kaylyn; Kilburn, David; Gross, Sean; Sudar, Damir; Bucher, Elmar; Nederlof, Michel; Dane, Mark; Gray, Joe W.; Heiser, Laura; Korkola, James.

In: Journal of visualized experiments : JoVE, No. 147, 21.05.2019.

Research output: Contribution to journalArticle

Smith, Rebecca ; Devlin, Kaylyn ; Kilburn, David ; Gross, Sean ; Sudar, Damir ; Bucher, Elmar ; Nederlof, Michel ; Dane, Mark ; Gray, Joe W. ; Heiser, Laura ; Korkola, James. / Using Microarrays to Interrogate Microenvironmental Impact on Cellular Phenotypes in Cancer. In: Journal of visualized experiments : JoVE. 2019 ; No. 147.
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