Laboratory of Oral Surgical Pathology, School of Dentistry, Federal University of Bahia, Salvador, Brazil.
Cancer and Translational Medicine Research Unit, Faculty of Medicine, University of Oulu, Oulu, Finland; Medical Research Center Oulu, Oulu University Hospital, University of Oulu, Oulu, Finland.
Arch Oral Biol. 2023 Jun;150:105675. doi: 10.1016/j.archoralbio.2023.105675. Epub 2023 Mar 16.
Cholesterol is a key lipid molecule within cell membranes. This is especially true in cavelolas, invaginated membrane nanodomains, which present the protein caveolin-1 (CAV-1). It is important to note that this structure is involved in many cell signalling pathways. Additionally, high cholesterol is seen in different tumor types but little is known in regards to oral tongue squamous cell carcinoma (OTSCC). The aim of this study was to evaluate the influence of cholesterol depletion on primary (SCC-25) and metastatic (HSC-3) OTSCC cell lines.
Cell membrane fluidity, cell viability, gene and protein expression of CAV-1 and of epithelial-mesenchymal transition (EMT) markers, cell migration in Myogel and invasion-myoma assay were evaluated after cholesterol depletion with methyl-β-cyclodextrin (MβCD - 7.5, 10 or 15 mM) RESULTS: Decreased cell viability and increased membrane fluidity of SCC-25 cells was seen with cholesterol depletion but cell viability was less affected and there was no effect on membrane fluidity in HSC-3. Cholesterol depletion also decreased CAV-1 at 6 h but increased it after 24 h.; both epithelial and mesenchymal EMT genes were upregulated after 6 h, followed by downregulation at 24 h in SCC-25. In HSC-3, CAV-1 was downregulated, and E-cadherin gene (ECAD) was upregulated at 6 h. Only the protein β-catenin in SCC-25 was affected, and cell migration of both cell lines was decreased, affecting SCC-25 more intensely. The invasive capacity within human myoma organotypic model was increased in SCC-25 and decreased in HSC-3.
Cholesterol depletion affects CAV-1 and ECAD inversely. This affect also depends on cell type since the invasive capacity was augmented in primary cells while decreased in metastatic cells.
胆固醇是细胞膜内的关键脂质分子。在凹陷的膜纳米域 cavelolas 中尤其如此，凹陷的膜纳米域中存在蛋白质 caveolin-1 (CAV-1)。需要注意的是，这种结构参与了许多细胞信号通路。此外，不同的肿瘤类型中胆固醇含量升高，但关于口腔舌鳞状细胞癌 (OTSCC) 知之甚少。本研究旨在评估胆固醇耗竭对原发性 (SCC-25) 和转移性 (HSC-3) OTSCC 细胞系的影响。
用甲基-β-环糊精 (MβCD - 7.5、10 或 15 mM) 耗竭胆固醇后，评估细胞膜流动性、细胞活力、CAV-1 和上皮-间充质转化 (EMT) 标志物的基因和蛋白表达、Myogel 中的细胞迁移和侵袭-肌瘤测定。
胆固醇耗竭导致 SCC-25 细胞活力降低和膜流动性增加，但对 HSC-3 细胞活力影响较小，对膜流动性无影响。胆固醇耗竭也使 CAV-1 在 6 小时减少，但在 24 小时后增加；SCC-25 中，6 小时后上皮和间充质 EMT 基因均上调，24 小时后下调。在 HSC-3 中，CAV-1 下调，E-钙粘蛋白基因 (ECAD) 上调 6 小时。仅 SCC-25 中的蛋白 β-连环蛋白受到影响，两种细胞系的细胞迁移均减少，对 SCC-25 的影响更为强烈。在人肌瘤器官型模型中，SCC-25 的侵袭能力增加，HSC-3 的侵袭能力降低。
胆固醇耗竭会对 CAV-1 和 ECAD 产生相反的影响。这种影响还取决于细胞类型，因为原发性细胞的侵袭能力增强，而转移性细胞的侵袭能力降低。
