Department of Physiology, Faculty of Medicine, University of Thessaly, BIOPOLIS, Larissa, Greece.
Department of Respiratory Medicine, Faculty of Medicine, University of Thessaly, BIOPOLIS, Larissa, Greece.
Clin Exp Pharmacol Physiol. 2021 Apr;48(4):543-552. doi: 10.1111/1440-1681.13446. Epub 2020 Dec 17.
Malignant pleural mesothelioma (MPM) is an aggressive tumour that grows in the pleural cavity. MPM spheroids released in the pleural fluid can form new tumour foci. Cell-cell, cell-extracellular matrix (ECM) interactions in 2D and 3D impact malignant cell behaviour during cell adhesion, migration, proliferation and epithelial-mesenchymal transition (EMT). In this study, epithelioid, biphasic and sarcomatoid MPM cell types as well as benign mesothelial cells were tested with regards to the above phenotypes. Fibronectin (FN) and homologous cell-derived extracellular matrix (hcd-ECM) treated substratum differentially affected the above phenotypes. 3D MPM spheroid invasion was higher in FN-collagen matrices in the epithelioid and biphasic cells, while 3D cell cultures of epithelioid and sarcomatoid MPM cells in FN-collagen showed a higher contractility compared to hcd-ECM-collagen. Cell aggregates demonstrated invasive behaviour in hcd-ECM matrices alone. Our results suggest that ECM and the dimensionality affect malignant cell behaviour during cell culture studies.
恶性胸膜间皮瘤（MPM）是一种在胸膜腔内生长的侵袭性肿瘤。释放到胸腔液中的 MPM 球体可以形成新的肿瘤灶。在细胞黏附、迁移、增殖和上皮间质转化（EMT）过程中，2D 和 3D 中的细胞-细胞、细胞-细胞外基质（ECM）相互作用会影响恶性细胞的行为。在这项研究中，上皮样、双相和肉瘤样 MPM 细胞类型以及良性间皮细胞在上述表型方面都进行了测试。纤连蛋白（FN）和同源细胞衍生的细胞外基质（hcd-ECM）处理的基质对上述表型有不同的影响。在 FN-胶原基质中，上皮样和双相细胞的 3D MPM 球体侵袭性更高，而 FN-胶原中的上皮样和肉瘤样 MPM 细胞的 3D 细胞培养显示出比 hcd-ECM-胶原更高的收缩性。细胞聚集体在 hcd-ECM 基质中单独表现出侵袭行为。我们的结果表明，细胞外基质和维度会影响细胞培养研究中恶性细胞的行为。
