Breast adenocarcinoma-derived exosomes lower first-contact de-adhesion strength of adenocarcinoma cells to brain endothelial layer

Despite of advances in modern therapeutics, one of the most feared complications of cancer are brain metastases, which often cause life impairing profound neurological symptoms and premature death. Breast adenocarcinoma is among the leading “sources” of brain metastases. Since the central nervous system lacks a classical lymphatic circulation, invading metastatic cells can reach the brain parenchyma only through haematogenous routes and must breach the blood-brain barrier (BBB). The key step before the transmigration of metastatic cells through the highly regulated interface of the BBB is the establishment of firm adhesion between the tumor cell and the cerebral endothelial layer. Using atomic force microscopy, as a high resolution force spectrograph, direct measurements of intercellular interactions was performed between living adenocarcinoma cells and a confluent endothelial layer pre-treated with carcinoma cell-derived exosomes. By immobilization of a living adenocarcinoma cell to an atomic force microscope’s cantilever, intercellular de-adhesions were directly measured by single cell force spectroscopy (SCFS) at quasi-physiological conditions. De-adhesion dynamics and strength was characterized by several different calculated parameters, involving aspects of both membrane and cell surface related factors. Our results indicate that de-adhesion strength was lower in case of exosome pre-treated endothelial cells as compared to non-treated controls. Breast adenocarcinoma-derived exosomes have direct effect on de-adhesion pattern of brain endothelium.