Granulocyte-macrophage colony-stimulating factor signals for increased glucose uptake in human melanoma cells Journal Article


Authors: Spielholz, C.; Heaney, M. L.; Morrison, M. E.; Houghton, A. N.; Vera, J. C.; Golde, D. W.
Article Title: Granulocyte-macrophage colony-stimulating factor signals for increased glucose uptake in human melanoma cells
Abstract: 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 α subunit of the GMR. Melanoma cell lines in early stages of differentiation expressed the largest quantities of α-subunit mRNA. Although five of these lines expressed trace levels of mRNA encoding the β 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 α 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 α subunit of the GMR can signal for increased glucose uptake in nonhematopoietic tumor cells.
Keywords: signal transduction; human cell; comparative study; polymerase chain reaction; cell proliferation; melanoma; gene expression; melanocyte; granulocyte macrophage colony stimulating factor; cell line; cell differentiation; tumor cells, cultured; molecular sequence data; kinetics; rna, messenger; leukemia, myeloid; melanoma cell; base sequence; receptor affinity; dna primers; tumor growth; glucose transport; dissociation constant; cytokine receptor; granulocyte-macrophage colony-stimulating factor; cytochalasin b; cell receptor; deoxyglucose; biological transport, active; receptors, granulocyte-macrophage colony-stimulating factor; monosaccharide transport proteins; human; priority journal; article; support, non-u.s. gov't; support, u.s. gov't, p.h.s.; macromolecular systems; cytochalasins
Journal Title: Blood
Volume: 85
Issue: 4
ISSN: 0006-4971
Publisher: American Society of Hematology  
Date Published: 1995-02-15
Start Page: 973
End Page: 980
Language: English
PUBMED: 7849318
PROVIDER: scopus
DOI: 10.1182/blood.V85.4.973.bloodjournal854973
DOI/URL:
Notes: Article -- Export Date: 28 August 2018 -- Source: Scopus
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MSK Authors
  1. Juan C Vera
    64 Vera
  2. Mark L Heaney
    94 Heaney
  3. David Golde
    127 Golde
  4. Alan N Houghton
    364 Houghton