GRANULOCYTE-MACROPHAGE COLONY-STIMULATING FACTOR SIGNALS FOR INCREASED GLUCOSE-UPTAKE IN HUMAN-MELANOMA CELLS

While the primary targets for granulocyte-macrophage colony-stimulatin g factor (GM-CSF) are hematopoietic precursors and mature myeloid cell s, GM-CSF receptors (GMR) are also found on normal tissues including p lacenta, endothelium, and oligodendrocytes as well as certain malignan t cells. The function of GMR in these nonhematopoietic cells is unknow n. 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-18 8, SK-MEL-23, SK-MEL-22, and SK-MEL-22A) expressed mRNA encoding the m embrane-bound and soluble isoforms of the alpha subunit of the GMR. Me lanoma cell lines in early stages of differentiation expressed the lar gest quantities of alpha-subunit mRNA. Although five of these lines ex pressed trace levels of mRNA encoding the beta subunit of the GMR. Sca tchard 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 wit h 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 stimu lated 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. Stimul ation of glucose uptake was transient, with maximum stimulation occurr ing at approximately 30 minutes in the presence of 1 nmol/L GM-CSF. GM -CSF stimulated glucose uptake 1.4- to 5.0-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 subun it of the GMR can signal for increased glucose uptake in nonhematopoie tic tumor cells. (C) 1995 by The American Society of Hematology.