De-adhesion dynamics of melanoma cells from brain endothelial layer

Biochim Biophys Acta Gen Subj. 2018 Mar;1862(3):745-751. doi: 10.1016/j.bbagen.2017.10.013. Epub 2017 Oct 21.

Abstract

Metastasis formation is a complex and not entirely understood process. The poorest prognosis and the most feared complications are associated to brain metastases. Melanoma derived brain metastases show the highest prevalence. Due to the lack of classical lymphatic drainage, in the process of brain metastases formation the haematogenous route is of primordial importance. The first and crucial step in this multistep process is the establishment of firm adhesion between the blood travelling melanoma cells and the tightly connected layer of the endothelium, which is the fundamental structure of the blood-brain barrier. This study compares the de-adhesion properties and dynamics of three melanoma cells types (WM35, A2058 and A375) to a confluent layer of brain micro-capillary endothelial cells. Cell type dependent adhesion characteristics are presented, pointing towards the existence of metastatic potential related nanomechanical aspects. Apparent mechanical properties such as elasticity, maximal adhesion force, number, size and distance of individual rupture events showed altered values pointing towards cell type dependent aspects. Our results underline the importance of mechanical details in case of intercellular interactions. Nevertheless, it suggests that in adequate circumstances elastic and adhesive characterizations might be used as biomarkers.

Keywords: Atomic force microscope; Cell mechanics; Cerebral endothelial cell; Melanoma cell adhesion; Metastatic potential; Single-cell force spectroscopy.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Blood-Brain Barrier
  • Brain / pathology*
  • Cell Adhesion
  • Cell Line, Tumor
  • Elastic Modulus
  • Elasticity
  • Endothelium / pathology*
  • Humans
  • Lymphatic Metastasis / pathology
  • Male
  • Melanoma / pathology*
  • Microscopy, Atomic Force
  • Neoplasm Invasiveness
  • Neoplasm Metastasis / pathology*
  • Stress, Mechanical