International Center for Materials Nanoarchitectonics (MANA) , National Institute for Materials Science , 1-1 Namiki , Tsukuba , Ibaraki 305-0044 , Japan.
Sorbonne Université, UMR 168, Institut Curie , 26 rue d'Ulm , 75248 Paris , Cedex 05 , France.
Langmuir. 2019 Jun 11;35(23):7396-7404. doi: 10.1021/acs.langmuir.8b01736. Epub 2018 Jul 19.
Controlling the propagation of primary tumors is fundamental to avoiding the epithelial to mesenchymal transition process leading to the dissemination and seeding of tumor cells throughout the body. Here we demonstrate that nanoparticles (NPs) limit the propagation of cell aggregates of CT26 murine carcinoma cells used as tumor models. The spreading behavior of these aggregates incubated with NPs is studied on fibronectin-coated substrates. The cells spread with the formation of a cell monolayer, the precursor film, around the aggregate. We study the effect of NPs added either during or after the formation of aggregates. We demonstrate that, in both cases, the spreading of the cell monolayer is slowed down in the presence of NPs and occurs only above a threshold concentration that depends on the size and surface chemistry of the NPs. The density of cells in the precursor films, measured by confocal microscopy, shows that the NPs stick cells together. The mechanism of slowdown is explained by the increase in cell-cell interactions due to the NPs adsorbed on the membrane of the cells. The present results demonstrate that NPs can modulate the collective migration of cells; therefore, they may have important implications for cancer treatment.
控制原发性肿瘤的增殖对于避免上皮间质转化过程至关重要，该过程会导致肿瘤细胞在全身扩散和播种。在这里，我们证明了纳米颗粒（NPs）可以限制用作肿瘤模型的 CT26 鼠癌细胞聚集物的增殖。在纤连蛋白涂层的基底上研究了与 NPs 孵育的这些聚集物的扩散行为。细胞在聚集物周围形成细胞单层，即前体膜，展开。我们研究了在聚集物形成过程中添加 NPs 或在聚集物形成后添加 NPs 的效果。我们证明，在这两种情况下，在存在 NPs 的情况下，细胞单层的铺展速度都会减慢，并且仅在取决于 NPs 的尺寸和表面化学性质的阈值浓度以上才会发生。通过共聚焦显微镜测量的前体膜中细胞的密度表明，NPs 将细胞粘在一起。速度减慢的机制可以解释为由于 NPs 吸附在细胞膜上，细胞间相互作用增加。目前的结果表明，NPs 可以调节细胞的集体迁移；因此，它们可能对癌症治疗具有重要意义。
