Direct mapping of melanoma cell – endothelial cell interactions

The most life-threatening aspect of cancer is metastasis; cancer patient mortality is mainly due to metastasis. Among all metastases, presence of brain metastasis is one with the poorest prognosis; the median survival time can be counted in months. Therefore, prevention or decreasing their incidence would be highly desired both by patients and physicians. Since the central nervous system (CNS) lacks classical lymphatic circulation, metastatic cells invading the CNS must breach the blood-brain barrier. The key step in this process is the establishment of firm adhesion between the cancer cell and the cerebral endothelial layer. Using the atomic force microscope, a high resolution force-spectrograph, our aim was to explore the connections among the cell morphology, cellular mechanics and biological function in the process of transendothelial migration of metastatic cancer cells. By immobilization of a melanoma cell to an atomic force microscope’s cantilever, intercellular adhesion was directly measured at quasi-physiological conditions. Hereby we present our latest results using this melanoma -decorated probe. Binding characteristics to a confluent layer of brain endothelial cells was directly measured by means of single cell force spectroscopy. Adhesion dynamics and strength was characterized and we present data about spatial distribution of elasticity and detachment strength. These results highlight the importance of cellular mechanics in brain metastasis formation and emphasize the enormous potential towards exploration of intercellular dynamics related processes