Comparison of metabolic pathways between cancer cells and stromal cells in colorectal carcinomas: a metabolic survival role for tumor-associated stroma.
Understanding tumor metabolism is important for the development of anticancer therapies. Immunohistochemical evaluation of colorectal adenocarcinomas showed that cancer cells share common enzyme/transporter activities suggestive of an anaerobic metabolism [high lactate dehydrogenase 5 (LDH5)/hypoxia-inducible factor alphas (HIFalphas)] with high ability for glucose absorption and lactate extrusion [high glucose transporter 1 (GLUT1)/monocarboxylate transporter (MCT1)]. The tumor-associated fibroblasts expressed proteins involved in lactate absorption (high MCT1/MCT2), lactate oxidation (high LDH1 and low HIFalphas/LDH5), and reduced glucose absorption (low GLUT1). The expression profile of the tumor-associated endothelium indicated aerobic metabolism (high LDH1 and low HIFalphas/LDH5), high glucose absorption (high GLUT1), and resistance to lactate intake (lack of MCT1). It is suggested that the newly formed stroma and vasculature express complementary metabolic pathways, buffering and recycling products of anaerobic metabolism to sustain cancer cell survival. Tumors survive and grow because they are capable of organizing the regional fibroblasts and endothelial cells into a harmoniously collaborating metabolic domain.
Koukourakis
Michael I
MI
Department of Radiotherapy/Oncology, Democritus University of Thrace, PO Box 12, Alexandroupolis 68100, Greece. targ@her.forthnet.gr
Giatromanolaki
Alexandra
A
Harris
Adrian L
AL
Sivridis
Efthimios
E
D000230:Adenocarcinoma / Q000378:metabolism*; D018797:Cell Cycle Proteins / Q000096:biosynthesis / Q000502:physiology; D015687:Cell Hypoxia; D049109:Cell Proliferation; D002470:Cell Survival; D003106:Colon / Q000166:cytology / Q000502:physiology; D015179:Colorectal Neoplasms / Q000378:metabolism*; D042783:Endothelial Cells / Q000502:physiology; D005347:Fibroblasts / Q000502:physiology; D020869:Gene Expression Profiling; D005947:Glucose / Q000378:metabolism*; D051246:Glucose Transport Proteins, Facilitative / Q000096:biosynthesis / Q000502:physiology; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000096:biosynthesis / Q000378:metabolism; D007150:Immunohistochemistry; D007527:Isoenzymes / Q000096:biosynthesis / Q000378:metabolism; D007770:L-Lactate Dehydrogenase / Q000096:biosynthesis / Q000378:metabolism; D000080864:Lactate Dehydrogenase 5; D019344:Lactic Acid / Q000378:metabolism; D027501:Monocarboxylic Acid Transporters / Q000096:biosynthesis / Q000502:physiology; D015513:Oncogene Proteins / Q000096:biosynthesis / Q000502:physiology; D017154:Stromal Cells / Q000378:metabolism*
D018797:Cell Cycle Proteins; D051246:Glucose Transport Proteins, Facilitative; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D007527:Isoenzymes; C115081:MCTS1 protein, human; D027501:Monocarboxylic Acid Transporters; D015513:Oncogene Proteins; C490427:SLC16A7 protein, human; D019344:Lactic Acid; D007770:L-Lactate Dehydrogenase; D000080864:Lactate Dehydrogenase 5; D005947:Glucose