A gentle approach to investigate the influence of LRP-1 silencing on the migratory behavior of breast cancer cells by atomic force microscopy and dynamic cell studies

Nanomedicine. 2019 Jun:18:359-370. doi: 10.1016/j.nano.2018.10.012. Epub 2018 Nov 10.

Abstract

The aim of the study was to get more insight into the role of LRP-1 in the mechanism of tumor progression in triple negative breast cancer. Atomic force microscopy, videomicroscopy, confocal microscopy and Rho-GTPAse activity assay were used on MDA-MB-231 and LRP-1-silenced cells. Silencing of LRP-1 in MDA-MB-231 cells was shown to led to a dramatic increase in the Young's modulus in parallel to a spectacular drop in membrane extension dynamics as well as a decrease in the cells migration abilities on both collagen I and fibronectin substrates. These results were perfectly correlated to a corresponding change in cell morphology and spreading capacity as well as in Rho-GTPases activity. By a multi-technique approach, it was demonstrated that LRP-1 played a crucial role in the migration of MDA-MB-231 cells by modulating the membrane extension dynamic. The originality of this AFM investigation lies in the non-invasive aspect of the measurements.

Keywords: Atomic force microscopy; LRP-1; Triple negative breast cancer.

MeSH terms

  • Animals
  • Breast Neoplasms / pathology*
  • Cattle
  • Cell Line, Tumor
  • Cell Movement*
  • Collagen Type II / metabolism
  • Elastic Modulus
  • Female
  • Fibronectins / metabolism
  • Gene Silencing
  • Humans
  • Low Density Lipoprotein Receptor-Related Protein-1 / metabolism*
  • Microscopy, Atomic Force / methods*
  • rho GTP-Binding Proteins / metabolism

Substances

  • Collagen Type II
  • Fibronectins
  • LRP1 protein, human
  • Low Density Lipoprotein Receptor-Related Protein-1
  • rho GTP-Binding Proteins