Monosomy-3 in
uveal melanoma (UM) cells increases the risk of fatal
metastases. The gene encoding the low-affinity
glucose transporter GLUT2 resides on chromosome 3q26.2. Here, we analyzed the expression of the
glucose transporters GLUT1, GLUT2, and GLUT3 with regard to the histological and clinical factors by performing immunohistochemistry on the primary
tumors of n = 33 UM patients. UMs with monosomy-3 exhibited a 57% lower immunoreactivity for GLUT2 and a 1.8×-fold higher ratio of GLUT1 to total GLUT1-3. The combined levels of GLUT1-3
proteins were reduced in the irradiated but not the non-irradiated
tumors with monosomy-3. GLUT3 expression was stronger in the irradiated samples with disomy-3 versus monosomy-3, but the ratio of the GLUT3
isoform to total GLUT1-3 did not differ with regard to the monosomy-3 status in the irradiated or non-irradiated subgroups. Systemic
metastases were associated with the presence of monosomy-3 in the primary and
circulating tumor cells as well as a higher GLUT1 ratio. Upregulation of the high-affinity
glucose transporter GLUT1 possibly as a compensation for the low-affinity
isoform GLUT2 may be enhancing the basal
glucose uptake in the UM cells with monosomy-3. Prevention of
hyperglycemia might, therefore, be a valuable approach to delay the lethal UM
metastases.