Z Gastroenterol 2012; 50 - P5_27
DOI: 10.1055/s-0031-1295983

GLUT 1 expression favors formation and growth of hepatic metastasis

A Koch 1, A Bosserhoff 2, C Hellerbrand 1
  • 1Department of Internal Medicine I, University Hospital Regensburg, Regensburg
  • 2Institut für Pathologie, Regensburg

High portal glucose levels may be one of the factors supporting tumor growth and progression in hepatic tissue, and we have previously shown that the facilitative glucose transporter (GLUT) 1 is a tumor-promotor in hepatocellular carcinoma, while its expression is at the detection limit in normal hepatocytes. The aim of this study was to analyze whether GLUT1 expression and a high capacity for glucose uptake, respectively, is a general pro-cancerogenic factor of the liver. For that, we used malignant melanoma as a model-tumor, which is known to preferentially metastasize to the liver. Methods and Results: Applying tissue micro array technology and GLUT1 immunohistochemistry we found that melanomas with hepatic metastasis revealed significantly higher GLUT1 expression than those without hepatic metastasis. To determine the functional role of GLUT1 in melanoma cells, we generated cell clones of the melanoma cell line B16, which stable expressed GLUT1 siRNA and which showed markedly suppressed GLUT1 expression compared to mock transfected controls. GLUT1 suppression caused significantly reduced glucose uptake and anaerobic glycolysis of melanoma cells. B16 cell clones with and without GLUT1 suppression were subjected to an established model of hepatic metastasis, in which tumor cells were injected into the spleen from where they metastasize into the liver via the portal circulation and form hepatic tumors. GLUT1 suppressed cells formed significantly smaller and less invasive metastasis than mock-transfected controls. Neither in vitro nor in vivo GLUT1 suppression caused a compensatory up-regulation of GLUT2, 3 or 4. Conclusion: Our data promote the hypothesis that high glucose levels in the portal circulation and the liver, and the capacity to utilize those, respectively, promote hepatic tumorigenesis and progression. GLUT1, which is almost selectively expressed in malignant cells but not in healthy liver, appears as attractive therapeutic target for hepatic tumors.