Granulocyte-macrophage colony-stimulating factor signals for increased glucose uptake in human melanoma cells.
While the primary targets for granulocyte-macrophage colony-stimulating factor (GM-CSF) are hematopoietic precursors and mature myeloid cells, GM-CSF receptors (GMR) are also found on normal tissues including placenta, endothelium, and oligodendrocytes as well as certain malignant cells. The function of GMR in these nonhematopoietic cells is unknown. We studied the function of GMR in human melanoma cell lines. Six of seven cell lines tested (clones 1-5 and 3.44 of SK-MEL-131, SK-MEL-188, SK-MEL-23, SK-MEL-22, and SK-MEL-22A) expressed mRNA encoding the membrane-bound and soluble isoforms of the alpha subunit of the GMR. Melanoma cell lines in early stages of differentiation expressed the largest quantities of alpha-subunit mRNA. Although five of these lines expressed trace levels of mRNA encoding the beta subunit of the GMR, Scatchard analysis of equilibrium binding data derived from three of the cell lines showed that they expressed only low-affinity GMR. Clones 3.44 and 1-5 of SK-MEL-131, and SK-MEL-188 cells expressed receptors with a dissociation constant (kd) for GM-CSF in the following ranges: 0.7 to 0.8, 1.2 to 1.8, and 0.4 to 0.8 nmol/L, respectively. GM-CSF stimulated glucose uptake in four of the melanoma cell lines expressing the alpha subunit, presumably through facilitative glucose transporters, as uptake was blocked by cytochalasin B but not cytochalasin E. Stimulation of glucose uptake was transient, with maximum stimulation occurring at approximately 30 minutes in the presence of 1 nmol/L GM-CSF. GM-CSF stimulated glucose uptake 1.4- to 2.0-fold but did not stimulate cell proliferation. These results suggest a metabolic role for the low-affinity GMR in melanoma cell lines and indicate that the alpha subunit of the GMR can signal for increased glucose uptake in nonhematopoietic tumor cells.
Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY 10021.
C
C
Spielholz
M L
ML
Heaney
M E
ME
Morrison
A N
AN
Houghton
J C
JC
Vera
D W
DW
Golde
D001483:Base Sequence; D001693:Biological Transport, Active; D002460:Cell Line; D003571:Cytochalasin B / Q000494:pharmacology; D003572:Cytochalasins / Q000494:pharmacology; D017931:DNA Primers; D003847:Deoxyglucose / Q000378:metabolism; D015870:Gene Expression; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000378:metabolism / Q000494:pharmacology*; D006801:Humans; D007700:Kinetics; D007951:Leukemia, Myeloid; D046911:Macromolecular Substances; D008545:Melanoma / Q000378:metabolism*; D008969:Molecular Sequence Data; D009004:Monosaccharide Transport Proteins / Q000187:drug effects / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000096:biosynthesis; D016187:Receptors, Granulocyte-Macrophage Colony-Stimulating Factor / Q000096:biosynthesis* / Q000502:physiology; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D014407:Tumor Cells, Cultured
D003572:Cytochalasins; D017931:DNA Primers; D046911:Macromolecular Substances; D009004:Monosaccharide Transport Proteins; D012333:RNA, Messenger; D016187:Receptors, Granulocyte-Macrophage Colony-Stimulating Factor; C007215:cytochalasin E; D003571:Cytochalasin B; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D003847:Deoxyglucose