TY - JOUR
T1 - Monosomy-3 alters the expression profile of the glucose transporters glut1-3 in uveal melanoma
AU - Maaßen, Tjorge
AU - Vardanyan, Siranush
AU - Brosig, Anton
AU - Merz, Hartmut
AU - Ranjbar, Mahdy
AU - Kakkassery, Vinodh
AU - Grisanti, Salvatore
AU - Tura, Aysegül
N1 - Funding Information:
Funding: This research was funded by the WERNER UND KLARA KREITZ-STIFTUNG, Kiel, Germany, grant number F279097 and the UNIVERSITY CLINIC LüBECK, Germany, grant number FC20222.
Publisher Copyright:
© 2020 by the authors. Licensee MDPI, Basel, Switzerland.
Copyright:
Copyright 2020 Elsevier B.V., All rights reserved.
PY - 2020/12/2
Y1 - 2020/12/2
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85097528950&partnerID=8YFLogxK
U2 - 10.3390/ijms21249345
DO - 10.3390/ijms21249345
M3 - Journal articles
C2 - 33302435
AN - SCOPUS:85097528950
SN - 1661-6596
VL - 21
SP - 1
EP - 19
JO - International Journal of Molecular Sciences
JF - International Journal of Molecular Sciences
IS - 24
M1 - 9345
ER -