Centro de Investigación en Medicina Traslacional "Severo Amuchástegui" (CIMETSA), Instituto Universitario Ciencias Biomédicas Córdoba (IUCBC), Naciones Unidas 420, Córdoba, Argentina.
Instituto de Investigación Médica Mercedes y Martín Ferreyra, INIMEC-CONICET-Universidad Nacional de Córdoba, Córdoba, Argentina.
Sci Rep. 2021 Jul 22;11(1):14984. doi: 10.1038/s41598-021-94399-8.
Fatty acids (FA) have a multitude of biological actions on living cells. A target of their action is cell motility, a process of critical importance during cancer cell dissemination. Here, we studied the effect of unsaturated FA on ovarian cancer cell migration in vitro and its role in regulating cytoskeleton structures that are essential for cell motility. Scratch wound assays on human ovary cancer SKOV-3 cell monolayers revealed that low doses (16 μM) of linoleic acid (LA, 18:2 ω6) and oleic acid (OA; 18:1 ω9) promoted migration, while α-linolenic acid (ALA, 18:3 ω3), showed a migration rate similar to that of the control group. Single cell tracking demonstrated that LA and OA-treated cells migrated faster and were more orientated towards the wound closure than control. In vitro addition of those FA resulted in an increased number, length and protrusion speed of filopodia and also in a prominent and dynamic lamellipodia at the cell leading edge. Using time-lapse video-microscopy and FRAP we observed an increase in both the speed and frequency of actin waves associated with more mobile actin and augmented Rac1 activity. We also observed that FA induced microtubule-organizing center (MTOC)-orientation towards the cell front and affected the dynamics of microtubules (MT) in the direction of cell migration. We propose that environmental cues such as OA and LA present in ascitic fluid, should be taken into account as key factors for the regulation of cell migration.
脂肪酸 (FA) 对活细胞具有多种生物学作用。它们的作用靶点之一是细胞迁移，这是癌细胞扩散过程中至关重要的一个过程。在这里，我们研究了不饱和脂肪酸对体外卵巢癌细胞迁移的影响及其在调节细胞迁移所必需的细胞骨架结构中的作用。在单层人类卵巢癌细胞 SKOV-3 的划痕实验中发现，低剂量（16μM）的亚油酸（LA，18:2 ω6）和油酸（OA；18:1 ω9）促进迁移，而α-亚麻酸（ALA，18:3 ω3）的迁移率与对照组相似。单细胞跟踪表明，与对照组相比，LA 和 OA 处理的细胞迁移更快，并且更朝向伤口闭合方向。体外添加这些 FA 导致丝状伪足的数量、长度和突起速度增加，并且在细胞前缘形成明显且动态的片状伪足。通过延时视频显微镜和 FRAP 观察到，与更活跃的肌动蛋白相关联的肌动蛋白波的速度和频率都增加了，并且 Rac1 活性也增强了。我们还观察到，FA 诱导微管组织中心（MTOC）朝向细胞前缘的定向，并影响微管（MT）在细胞迁移方向上的动态。我们提出，腹水中存在的 OA 和 LA 等环境线索应被视为调节细胞迁移的关键因素。
