Proteome of Hypoxic Glioblastoma Cells

ABSTRACT: Tumors are known for hypoxic microenvironment due to decreased hemoglobin oxygen saturation arising from high acidity in tumor tissue, high consumption rates of rapidly proliferating cells, and irregular or even short-time cessation of blood flow in deformed vessels. Consequently, hypoxia promotes tumor to be highly malignant, metastatic, and resistant to therapy. In order to better understand the mechanisms of the correlation between hypoxia and cancer progression, we have studied the proteome of glioblastoma cells grown for five successive days under 1% oxygen via an innovative strategy, which involves quantification of newly synthesized proteins from cells previously labeled with heavy stable-isotope arginine and real-time accurate assessment of cell replication through the arginine light/heavy ratio in histone peptides. We found that hypoxia affects cancer cells in three sequential stages in vitro: the early inflammatory response stage with highly over-expressed glucose transporter protein GLUT1 and inflammation marker MKP2; the pre-EMT stage with over-expression of literally all enzymes in the glycolysis pathway towards pyruvate, as well as vitamin B12 transporter protein TCN2 which is essential for one-carbon metabolism; and the last EMT stage with distinct morphologic changes and protein expression profiles. Expression of methylation enzymes and the cellular production of their cofactors are either revealed or predicted to be significantly influenced by hypoxia, which demonstrates the importance of a follow-up study on epigenetic reprogramming in hypoxic cells.

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Permanent Cell Line Cell, Cell Culture

DISEASE(S): Brain Glioblastoma Multiforme

SUBMITTER: Kangling Zhang  

LAB HEAD: Kangling Zhang

PROVIDER: PXD005487 | Pride | 2017-09-12

REPOSITORIES: Pride