School of Biological Sciences, University of the Punjab, Quaid-i-Azam Campus, Lahore 54590, Pakistan; Cancer Research Center, University of the Punjab, Quaid-i-Azam Campus, Lahore 54590, Pakistan; Centre for Research in Molecular Medicines, University of Lahore, 1-km Defence Road, Lahore, 54000, Pakistan.
School of Biological Sciences, University of the Punjab, Quaid-i-Azam Campus, Lahore 54590, Pakistan; Cancer Research Center, University of the Punjab, Quaid-i-Azam Campus, Lahore 54590, Pakistan.
Crit Rev Eukaryot Gene Expr. 2021;31(6):23-36. doi: 10.1615/CritRevEukaryotGeneExpr.2021039789.
Cell adhesion is the backbone of many events in the cancer cell life cycle, including proliferation, metastasis, migration, invasion and even cell survival. In a tumor, usually the cells in the core have high migratory potential though they constantly suffer from glucose starvation. Our study was aimed at understanding events such as attachment to the surfaces at one site and then mobility to the secondary sites during progression of cancer in the hormone sensitive breast cancer cells MCF7, following their exposure to different concentrations of glucose in the environment. We have shown that low glucose availability is detected within 3 h of shortage which is then translated into variable expression of genes for cell-to-cell adhesion such as cadherins and Ig-like cell adhesion molecules, and matrix-associated genes such as integrins and metalloproteases. We also found that low glucose concentrations induced cell adhesion, whereas higher concentrations stimulated cell migration. In addition, several regulatory molecules involved in mitochondrial metabolism, proliferation, and glucose uptake as demonstrated respectively by MTT assay, BrdU uptake, glucose uptake and pyruvate kinase activity showed varied expression during epithelial to mesenchymal transition. Cytoskeleton staining demonstrated development of lamellipodia in glucose starved medium indicating cascade of physiological and molecular events in the cells to find a more nutrient-rich environment for the development of secondary tumor. Further studies on protein markers with a 3D spheroid culturing approach are likely to expand our understanding of onset of metastasis in tumor tissues.
细胞黏附是癌症细胞生命周期中许多事件的基础，包括增殖、转移、迁移、侵袭，甚至细胞存活。在肿瘤中，尽管核心细胞经常遭受葡萄糖饥饿，但通常具有高迁移潜力。我们的研究旨在了解激素敏感型乳腺癌细胞 MCF7 在癌症进展过程中的事件，例如在暴露于环境中不同浓度的葡萄糖后，在一个部位附着，然后移动到次要部位。我们已经表明，低葡萄糖供应在短缺后 3 小时内被检测到，然后转化为细胞间黏附基因（如钙黏蛋白和 Ig 样细胞黏附分子）和基质相关基因（如整合素和金属蛋白酶）的可变表达。我们还发现低葡萄糖浓度诱导细胞黏附，而较高浓度刺激细胞迁移。此外，涉及线粒体代谢、增殖和葡萄糖摄取的几种调节分子如 MTT 测定法、BrdU 摄取、葡萄糖摄取和丙酮酸激酶活性所示，在上皮间质转化过程中表现出不同的表达。细胞骨架染色显示在葡萄糖饥饿培养基中形成了片状伪足，表明细胞中发生了一系列生理和分子事件，以寻找更富含营养的环境来发展继发性肿瘤。通过 3D 球体培养方法研究蛋白质标志物可能会进一步加深我们对肿瘤组织中转移发生的理解。
