Institute of Biophysics, Biological Research Centre, Szeged, Hungary.
Institute of Biophysics, Biological Research Centre, Szeged, Hungary; Theoretical Medicine Doctoral School, University of Szeged, Szeged, Hungary.
Colloids Surf B Biointerfaces. 2021 Aug;204:111810. doi: 10.1016/j.colsurfb.2021.111810. Epub 2021 Apr 30.
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.
尽管现代治疗学取得了进步，但癌症最令人恐惧的并发症之一是脑转移，这常常导致危及生命的严重神经症状和过早死亡。乳腺腺癌是脑转移的主要“来源”之一。由于中枢神经系统缺乏经典的淋巴循环，侵袭性转移细胞只能通过血源性途径到达脑实质，并且必须突破血脑屏障（BBB）。转移细胞通过高度调节的 BBB 界面迁移的关键步骤是肿瘤细胞与脑内皮层之间建立牢固的粘附。原子力显微镜作为一种高分辨率力谱仪，用于对活腺癌细胞与用癌细胞衍生的外泌体预处理的汇合内皮层之间的细胞间相互作用进行直接测量。通过将活腺癌细胞固定到原子力显微镜的悬臂上，单细胞力谱学（SCFS）可以在准生理条件下直接测量细胞间去粘附。通过涉及膜和细胞表面相关因素的几个不同计算参数来表征去粘附动力学和强度。我们的结果表明，与未处理的对照组相比，经外泌体预处理的内皮细胞的去粘附强度较低。乳腺腺癌衍生的外泌体对脑内皮细胞的去粘附模式有直接影响。
