Monosomy-3 Alters the Expression Profile of the Glucose Transporters GLUT1-3 in Uveal Melanoma

International Journal of Molecular Sciences

Aysegül Tura¹  Salvatore Grisanti¹  Siranush Vardanyan¹  Mahdy Ranjbar¹  Vinodh Kakkassery¹  Anton Brosig¹  Tjorge Maaßen¹  Hartmut Merz² 

[1] Department of Ophthalmology, University of Lübeck, Ratzeburger Allee 160, 23538 Lübeck, Germany;Reference Center for Lymph Node Pathology and Haematopathology, 23562 Lübeck, Germany;

关键词: uveal melanoma;    monosomy-3;    glucose transport;    GLUT1;    GLUT2;    GLUT3;   

DOI  :  10.3390/ijms21249345

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown