Breast Cancer Cell Line Aggregate Morphology Does Not Predict Invasive Capacity

PLoS One. 2015 Sep 29;10(9):e0139523. doi: 10.1371/journal.pone.0139523. eCollection 2015.

Abstract

To invade and metastasize to distant loci, breast cancer cells must breach the layer of basement membrane surrounding the tumor and then invade through the dense collagen I-rich extracellular environment of breast tissue. Previous studies have shown that breast cancer cell aggregate morphology in basement membrane extract correlated with cell invasive capacity in some contexts. Moreover, cell lines from the same aggregate morphological class exhibited similarities in gene expression patterns. To further assess the capacity of cell and aggregate morphology to predict invasive capacity in physiologically relevant environments, six cell lines with varied cell aggregate morphologies were assessed in a variety of assays including a 3D multicellular invasion assay that recapitulates cell-cell and cell-environment contacts as they exist in vivo in the context of the primary breast tumor. Migratory and invasive capacities as measured through a 2D gap assay and a 3D spheroid invasion assay reveal that breast cancer cell aggregate morphology alone is insufficient to predict migratory speed in 2D or invasive capacity in 3D. Correlations between the 3D spheroid invasion assay and gene expression profiles suggest this assay as an inexpensive functional method to predict breast cancer invasive capacity.

Publication types

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

MeSH terms

  • Breast Neoplasms / genetics
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / pathology*
  • Cadherins / metabolism
  • Cell Aggregation
  • Cell Culture Techniques / methods*
  • Cell Line, Tumor
  • Cell Movement*
  • Collagen / metabolism
  • Female
  • Flow Cytometry
  • Gene Expression Profiling / methods
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Integrins / metabolism
  • Microscopy, Confocal
  • Neoplasm Invasiveness
  • Spheroids, Cellular*

Substances

  • Cadherins
  • Integrins
  • Collagen

Grants and funding

This work was supported by the National Science Foundation and the National Institutes of Health (http://www.nsf.gov/pubs/2012/nsf12514/nsf12514.htm) via PESO 1227297 to LJK. Additional funding provided by Columbia University through support of graduate student teaching assistants (MJZ) and through discretionary funds for LJK. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.