Aftab Saira, Shakoori Abdul Rauf
School of Biological Sciences, University of the Punjab, Quaid-i-Azam Campus, Lahore, Pakistan.
Department of Biochemistry, Faculty of Life Sciences, University of Central Punjab, Lahore, Pakistan.
J Cell Biochem. 2019 Oct;120(10):16824-16839. doi: 10.1002/jcb.28940. Epub 2019 May 20.
Studying the metabolic pathways of cancer cells is considered as a key to control cancer malignancies and open windows for effective drug discovery against cancer. Of all the properties of a tumor, metastasis potential is a defining characteristic. Metastasis is controlled by a variety of factors that directly control the expression of cell adhesion proteins. In this study we have investigated the expression of cell to cell and cell to matrix adhesion protein genes during the initial phases of attachment of human glioblastoma cancer cell line SF767 (66Y old human female: UCSF Neurosurgery Tissue Bank) to the attachment surface under (Cell culture treated polystyrene plate bottom) glucose-rich and glucose-starved conditions. The aim was to imitate the natural microenvironment of glucose availability to cancer cells inside a tumor that triggers epithelial to mesenchymal transition (EMT). In this study, we have observed the gene expression of epithelial and mesenchymal isoforms of cadherin (E-CAD and N-CAD) and Ig like cell adhesion molecules (E-CAM and N-CAM) along with Integrin family subunits for the initial attachment of cancer cells. We observed that high glucose environments promoted cell survival and cell adhesion, whereas low glucose accelerated EMT by downregulating the expression level of integrin, E-CAD, and N-CAD, and upregulation of N-CAM during early period of cell adhesion. Low glucose availability also downregulated variety of structural and regulatory genes, such as zinc finger E-box binding home box 1A), cytokeratin, Snail, and β catenin, and upregulation of hypoxia-inducible factor 1, matrix metalloprotease 13/Collagenase 3, vimentim, p120, and fructose 1,6 bisphosphatase. Glucose conditions are more efficient for cancer studies in this case glioblastoma cells.
研究癌细胞的代谢途径被认为是控制癌症恶性肿瘤以及为有效抗癌药物研发打开新窗口的关键。在肿瘤的所有特性中，转移潜能是一个决定性特征。转移受多种直接控制细胞黏附蛋白表达的因素所调控。在本研究中，我们调查了人胶质母细胞瘤细胞系SF767（66岁女性：加州大学旧金山分校神经外科组织库）在富含葡萄糖和葡萄糖饥饿条件下（细胞培养处理过的聚苯乙烯板底部）附着于附着表面初始阶段细胞间和细胞与基质黏附蛋白基因的表达。目的是模拟肿瘤内癌细胞可利用葡萄糖的自然微环境，这种环境会引发上皮-间质转化（EMT）。在本研究中，我们观察了钙黏蛋白（E-CAD和N-CAD）以及免疫球蛋白样细胞黏附分子（E-CAM和N-CAM）的上皮和间质亚型的基因表达，以及整合素家族亚基在癌细胞初始附着过程中的表达。我们观察到高糖环境促进细胞存活和细胞黏附，而低糖环境在细胞黏附早期通过下调整合素、E-CAD和N-CAD的表达水平以及上调N-CAM来加速EMT。低糖可用性还下调了多种结构和调控基因，如锌指E盒结合同源框1A、细胞角蛋白、Snail和β连环蛋白，并上调了缺氧诱导因子1、基质金属蛋白酶13/胶原酶3、波形蛋白、p120和果糖1,6-二磷酸酶。在这种情况下，对于胶质母细胞瘤细胞的癌症研究而言，葡萄糖条件更为有效。
