title: Direct mapping of melanoma cell - endothelial cell interactions.
abstract: 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. Metastatic cells invading the brain must breach the cerebral vasculature, primarily 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 by 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 were 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 toward exploration of intercellular dynamic-related processes.
authors.affiliation: Institute of Biophysics, Biological Research Centre, Hungarian Academy of Sciences, Szeged, Hungary.|Laboratoire Charles Coulomb L2C, UMR 5221, CNRS, Université de Montpellier, Montpellier, France.
authors.forename: Béla
authors.initials: B
authors.lastname: Varga
authors.affiliation: Institute of Biophysics, Biological Research Centre, Hungarian Academy of Sciences, Szeged, Hungary.
authors.forename: Csilla
authors.initials: C
authors.lastname: Fazakas
authors.affiliation: Institute of Biophysics, Biological Research Centre, Hungarian Academy of Sciences, Szeged, Hungary.
authors.forename: Judit
authors.initials: J
authors.lastname: Molnár
authors.affiliation: Institute of Biophysics, Biological Research Centre, Hungarian Academy of Sciences, Szeged, Hungary.
authors.forename: Imola
authors.initials: I
authors.lastname: Wilhelm
authors.affiliation: Babes-Bolyai University, Faculty of Physics, Cluj-Napoca, Romania.
authors.forename: Réka A
authors.initials: RA
authors.lastname: Domokos
authors.affiliation: Institute of Biophysics, Biological Research Centre, Hungarian Academy of Sciences, Szeged, Hungary.|Institute of Life Sciences, Vasile Goldiş Western University, Arad, Romania.
authors.forename: István A
authors.initials: IA
authors.lastname: Krizbai
authors.affiliation: Institute of Biophysics, Biological Research Centre, Hungarian Academy of Sciences, Szeged, Hungary.
authors.forename: Zsolt
authors.initials: Z
authors.lastname: Szegletes
authors.affiliation: Institute of Biophysics, Biological Research Centre, Hungarian Academy of Sciences, Szeged, Hungary.
authors.forename: György
authors.initials: G
authors.lastname: Váró
authors.affiliation: Institute of Biophysics, Biological Research Centre, Hungarian Academy of Sciences, Szeged, Hungary.
authors.forename: Attila G
authors.identifier: 0000-0003-0524-0946
authors.initials: AG
authors.lastname: Végh
mesh_terms: D000328:Adult; D001696:Biomechanical Phenomena; D001812:Blood-Brain Barrier; D001921:Brain / Q000166:cytology / Q000473:pathology; D002448:Cell Adhesion; D002450:Cell Communication; D045744:Cell Line, Tumor; D002465:Cell Movement; D042783:Endothelial Cells / Q000166:cytology*; D006801:Humans; D008297:Male; D008545:Melanoma; D018625:Microscopy, Atomic Force; D059010:Single-Cell Analysis / Q000379:methods*
keywords: atomic force microscope; cancer; cell adhesion; cerebral endothelial cell; direct mapping; living cell; nanomechanics; single-cell force spectroscopy