Varga Béla, Fazakas Csilla, Molnár Judit, Wilhelm Imola, Domokos Réka A, Krizbai István A, Szegletes Zsolt, Váró György, Végh Attila G
Institute of Biophysics, Biological Research Centre, Hungarian Academy of Sciences, Szeged, Hungary.
Laboratoire Charles Coulomb L2C, UMR 5221, CNRS, Université de Montpellier, Montpellier, France.
J Mol Recognit. 2017 Jun;30(6). doi: 10.1002/jmr.2603. Epub 2016 Dec 23.
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.
癌症最危及生命的方面是转移；癌症患者的死亡主要归因于转移。在所有转移中，脑转移的预后最差；中位生存时间以月计算。因此，患者和医生都非常希望预防或降低其发生率。侵入大脑的转移细胞必须突破脑血管系统，主要是血脑屏障。这一过程的关键步骤是癌细胞与脑内皮细胞层之间建立牢固的粘附。我们使用原子力显微镜（一种高分辨率力谱仪），旨在探索转移癌细胞跨内皮迁移过程中细胞形态、细胞力学和生物学功能之间的联系。通过将黑色素瘤细胞固定在原子力显微镜的悬臂上，在准生理条件下直接测量细胞间粘附力。在此，我们展示使用这种装饰有黑色素瘤的探针所获得的最新结果。通过单细胞力谱直接测量与脑内皮细胞汇合层的结合特性。对粘附动力学和强度进行了表征，并给出了弹性和脱离强度空间分布的数据。这些结果突出了细胞力学在脑转移形成中的重要性，并强调了探索细胞间动态相关过程的巨大潜力。
