Minimization of thermodynamic costs in cancer cell invasion

Proc Natl Acad Sci U S A. 2013 Jan 29;110(5):1686-91. doi: 10.1073/pnas.1221147110. Epub 2013 Jan 14.

Abstract

Metastasis, the truly lethal aspect of cancer, occurs when metastatic cancer cells in a tumor break through the basement membrane and penetrate the extracellular matrix. We show that MDA-MB-231 metastatic breast cancer cells cooperatively invade a 3D collagen matrix while following a glucose gradient. The invasion front of the cells is a dynamic one, with different cells assuming the lead on a time scale of 70 h. The front cell leadership is dynamic presumably because of metabolic costs associated with a long-range strain field that precedes the invading cell front, which we have imaged using confocal imaging and marker beads imbedded in the collagen matrix. We suggest this could be a quantitative assay for an invasive phenotype tracking a glucose gradient and show that the invading cells act in a cooperative manner by exchanging leaders in the invading front.

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
  • Cell Culture Techniques
  • Cell Line, Tumor
  • Cell Movement*
  • Chemotaxis
  • Collagen / metabolism*
  • Extracellular Matrix / metabolism
  • Female
  • Glucose / metabolism*
  • Humans
  • Luminescent Proteins / genetics
  • Luminescent Proteins / metabolism
  • MCF-7 Cells
  • Microscopy, Confocal
  • Microscopy, Fluorescence
  • Neoplasm Invasiveness
  • Neoplasm Metastasis
  • Thermodynamics*
  • Time Factors
  • Tumor Microenvironment

Substances

  • Luminescent Proteins
  • Collagen
  • Glucose