Effects of Hypoxia on Invasion, Metabolism, Proliferation, Proteinase Activities and Gene Expression of a Human Prostate Cancer Cell Line
Artemov D, Bhujwalla Z, Ackerstaff E
Johns Hopkins University School of Medicine
Oxygen tensions below 10 mmHg in human tumors have been linked to decreased patient survival. Using our MR-compatible invasion assay, we demonstrated that despite increased endogenous activities of selected proteinases hypoxia can reduce cancer cell invasion. The presence of endothelial cells can ameliorate this reduction in invasion, which might be partly explained by their higher endogenous proteinase activities. In the cancer cells, hypoxia decreased cell proliferation and up- and down-regulated multiple genes related to invasion, angiogenesis, cell cycle and energy and lipid metabolism. Our MR results could not be explained solely by proteinase activity and gene expression changes, demonstrating the importance of combining gene and protein expression analysis with functional assays.