Glucose Stress Induces Early Onset of Metastasis in Hormone-Sensitive Breast Cancer Cells.

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.