C. Spielholz et al., GRANULOCYTE-MACROPHAGE COLONY-STIMULATING FACTOR SIGNALS FOR INCREASED GLUCOSE-UPTAKE IN HUMAN-MELANOMA CELLS, Blood, 85(4), 1995, pp. 973-980
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.