%0 Journal Article
%T Metabolic markers in relation to hypoxia; staining patterns and colocalization of pimonidazole, HIF-1¦Á, CAIX, LDH-5, GLUT-1, MCT1 and MCT4
%A Saskia E Rademakers
%A Jasper Lok
%A Albert J van der Kogel
%A Johan Bussink
%A Johannes HAM Kaanders
%J BMC Cancer
%D 2011
%I BioMed Central
%R 10.1186/1471-2407-11-167
%X 20 biopsies of advanced head and neck carcinomas were immunohistochemically stained and analyzed. All patients were given the hypoxia marker pimonidazole intravenously 2 h prior to biopsy taking. The tumor area positive for each marker, the colocalization of the different markers and the distribution of the markers in relation to the blood vessels were assessed by semiautomatic quantitative analysis.MCT1 staining was present in hypoxic (pimonidazole stained) as well as non-hypoxic areas in almost equal amounts. MCT1 expression showed a significant overall correlation (r = 0.75, p < 0.001) and strong spatial relationship with CAIX. LDH-5 showed the strongest correlation with pimonidazole (r = 0.66, p = 0.002). MCT4 and GLUT-1 demonstrated a typical diffusion-limited hypoxic pattern and showed a high degree of colocalization. Both MCT4 and CAIX showed a higher expression in the primary tumor in node positive patients (p = 0.09 both).Colocalization and staining patterns of metabolic and hypoxia-related proteins provides valuable additional information over single protein analyses and can improve the understanding of their functions and environmental influences.Malignant tumors often exhibit an altered metabolism compared to normal tissues. This phenomenon can be explained by several underlying mechanisms. First of all, the genetic changes related to a high proliferation rate, as observed in many tumors, lead to an increased metabolism[1]. Another important reason for a changed metabolism is the adaptation of tumor cells to the microenvironment. Due to rapid tumor growth, hypoxic areas are frequently encountered. Under circumstances of severe hypoxia, cells are forced to use anaerobic glycolysis as their primary energy source, the Pasteur effect[2]. Normal cells convert to oxidative phosphorylation when oxygen levels are restored. In contrast, tumor cells can use aerobic glycolysis even in the presence of sufficient amounts of oxygen. This is called the Warburg effect,
%U http://www.biomedcentral.com/1471-2407/11/167