Abstract
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.
Highlights
Fatty acids (FA) have a multitude of biological actions on living cells
We focused on FA because they are components of the plasma membrane and some of their derivatives have been implicated in controlling cellular functions such as proliferation, apoptosis, migration[7] and carcinogenesis[8,9]
Metastatic ovarian cancer cells inhabit an environment enriched in factors that are likely to promote cell migration and spread of the disease[26,27]
Summary
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. 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. At the rear end of a migrating cell, the contractility of actomyosin, regulated by MT, is both required and needed for cell translocation In both domains, the front and the rear of a polarized migrating cell, several regulators modulate and coordinate the MT network and the activity of actin allowing them to drive cell migration[3]. The front and the rear of a polarized migrating cell, several regulators modulate and coordinate the MT network and the activity of actin allowing them to drive cell migration[3] It is a well-established fact that extracellular signals modify cell migration. We did not examine it in the present study
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