ERRMECe, Equipe de Recherche sur Les Relations Matrice Extracellulaire-Cellules (EA1391), Institut des Matériaux I-MAT (FD4122), CY Cergy Paris University, Maison Internationale de la Recherche, 1 Rue Descartes, 95000, Neuville sur Oise Cedex, France; RNA Molecular Biology, F.R.S./FNRS, Université Libre de Bruxelles, Charleroi, Gosselies, Belgium.
ERRMECe, Equipe de Recherche sur Les Relations Matrice Extracellulaire-Cellules (EA1391), Institut des Matériaux I-MAT (FD4122), CY Cergy Paris University, Maison Internationale de la Recherche, 1 Rue Descartes, 95000, Neuville sur Oise Cedex, France.
Biomaterials. 2021 Feb;269:120610. doi: 10.1016/j.biomaterials.2020.120610. Epub 2020 Dec 16.
An early fundamental step in ovarian cancer progression is the dissemination of cancer cells through liquid environments, one of them being cancer ascites accumulated in the peritoneal cavity. These biological fluids are highly crowded with a high total macromolecule concentration. This biophysical property of fluids is widely used in tissue engineering for a few decades now, yet is largely underrated in cancer biomimetic models. To unravel the role of fluids extracellular macromolecular crowding (MMC), we exposed ovarian cancer cells (OCC) to high molecular weight inert polymer solutions. High macromolecular composition of extracellular liquid presented a differential effect: i) it impeded non-adherent OCC aggregation in suspension and, decreased their adhesion; ii) it promoted adherent OCC migration by decreasing extracellular matrix deposition. Besides, there seemed to be a direct link between the extracellular MMC and intracellular processes, especially the actin cytoskeleton organization and the nucleus morphology. In conclusion, extracellular fluid MMC orients OCC dissemination phenotype. Integrating MMC seems crucial to produce more relevant mimetic 3D in vitro fluid models to study ovarian dissemination but also to screen drugs.
卵巢癌进展的早期基本步骤是癌细胞通过液体环境的传播，其中之一是积聚在腹腔中的癌症腹水。这些生物液体中含有很高的总大分子浓度，高度拥挤。几十年来，这种流体的生物物理特性已被广泛用于组织工程，但在癌症仿生模型中却被大大低估了。为了阐明细胞外大分子拥挤（MMC）对液体的作用，我们将卵巢癌细胞（OCC）暴露于高分子量惰性聚合物溶液中。细胞外液体的高分子组成产生了不同的影响：i）它阻止了悬浮液中非附着 OCC 的聚集，并降低了它们的粘附性；ii）它通过减少细胞外基质的沉积促进了附着的 OCC 迁移。此外，细胞外 MMC 似乎与细胞内过程之间存在直接联系，特别是肌动蛋白细胞骨架组织和细胞核形态。总之，细胞外流体 MMC 决定了 OCC 传播表型。整合 MMC 似乎对于产生更相关的模拟 3D 体外流体模型来研究卵巢扩散以及筛选药物至关重要。
