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Granulocyte-macrophage colony-stimulating factor signals for increased
glucose uptake in human melanoma cells
C Spielholz, ML Heaney, ME Morrison, AN Houghton, JC Vera and DW Golde
Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York,
NY 10021.
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.
Volume 85,
Issue 4,
pp. 973-980,
02/15/1995
Copyright © 1995 by The American Society of Hematology
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