Haemopoietic cell growth factor mediates cell survival via its action on glucose transport (original) (raw)
Abstract
A number of haematopoietic precursor cell lines have been established which exhibit an absolute dependence on haematopoietic cell growth factor (HCGF) which is secreted by WEHI-3 myelomonocytic leukaemia cells. In the presence of HCGF, ATP levels are maintained in these factor-dependent cells (FDC-P cells); in the absence of HCGF, intracellular ATP levels undergo a steady depletion. The cell death that follows this ATP depletion can be prevented by supplying exogenous ATP suggesting that HCGF maintains these cells via its effects on energy metabolism. We have investigated the effect of HCGF on FDC-P cells further and found that: (i) HCGF markedly and rapidly increases lactate production; (ii) high extracellular glucose or glycolytic intermediate concentrations can maintain FDC-P cell viability to some extent whilst stimulating lactate production; (iii) the uptake of 2-deoxyglucose by FDC-P2 cells is stimulated by HCGF in a dose-dependent fashion. This uptake is inhibited by cytochalasin B; (iv) HCGF does not stimulate L-glucose uptake by FDC-P cells. These results suggest that HCGF acts to maintain FDC-P cells via its action on glucose transport. The significance of these results to haemopoiesis and leukaemogenesis is discussed.

Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Bazill G. W., Haynes M., Garland J., Dexter T. M. Characterization and partial purification of a haemopoietic cell growth factor in WEHI-3 cell conditioned medium. Biochem J. 1983 Mar 15;210(3):747–759. doi: 10.1042/bj2100747. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Belt J. A., Thomas J. A., Buchsbaum R. N., Racker E. Inhibition of lactate transport and glycolysis in Ehrlich ascites tumor cells by bioflavonoids. Biochemistry. 1979 Aug 7;18(16):3506–3511. doi: 10.1021/bi00583a011. [DOI] [PubMed] [Google Scholar]
- Boyer P. D., Chance B., Ernster L., Mitchell P., Racker E., Slater E. C. Oxidative phosphorylation and photophosphorylation. Annu Rev Biochem. 1977;46:955–966. doi: 10.1146/annurev.bi.46.070177.004515. [DOI] [PubMed] [Google Scholar]
- Breen G. A., Scheffler I. E. Cytoplasmic inheritance of oligomycin resistance in Chinese hamster ovary cells. J Cell Biol. 1980 Sep;86(3):723–729. doi: 10.1083/jcb.86.3.723. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Burgess A. W., Metcalf D., Russell S. H., Nicola N. A. Granulocyte/macrophage-, megakaryocyte-, eosinophil- and erythroid-colony-stimulating factors produced by mouse spleen cells. Biochem J. 1980 Feb 1;185(2):301–314. doi: 10.1042/bj1850301. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Burk D., Woods M., Hunter J. On the significance of glucolysis for cancer growth, with special reference to Morris rat hepatomas. J Natl Cancer Inst. 1967 Jun;38(6):839–863. [PubMed] [Google Scholar]
- Bustamante E., Morris H. P., Pedersen P. L. Energy metabolism of tumor cells. Requirement for a form of hexokinase with a propensity for mitochondrial binding. J Biol Chem. 1981 Aug 25;256(16):8699–8704. [PubMed] [Google Scholar]
- Dexter T. M., Garland J., Scott D., Scolnick E., Metcalf D. Growth of factor-dependent hemopoietic precursor cell lines. J Exp Med. 1980 Oct 1;152(4):1036–1047. doi: 10.1084/jem.152.4.1036. [DOI] [PMC free article] [PubMed] [Google Scholar]
- HEYTLER P. G., PRICHARD W. W. A new class of uncoupling agents--carbonyl cyanide phenylhydrazones. Biochem Biophys Res Commun. 1962 May 4;7:272–275. doi: 10.1016/0006-291x(62)90189-4. [DOI] [PubMed] [Google Scholar]
- Harris M. Cytoplasmic transfer of resistance to antimycin A in Chinese hamster cells. Proc Natl Acad Sci U S A. 1978 Nov;75(11):5604–5608. doi: 10.1073/pnas.75.11.5604. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Inui K. I., Tillotson L. G., Isselbacher K. J. Hexose and amino acid transport by chicken embryo fibroblasts infected with temperature-sensitive mutant of Rous sarcoma virus. Comparison of transport properties of whole cells and membrane vesicles. Biochim Biophys Acta. 1980 Jun 6;598(3):616–627. doi: 10.1016/0005-2736(80)90041-3. [DOI] [PubMed] [Google Scholar]
- Iscove N. N., Roitsch C. A., Williams N., Guilbert L. J. Molecules stimulating early red cell, granulocyte, macrophage, and megakaryocyte precursors in culture: similarity in size, hydrophobicity, and charge. J Cell Physiol Suppl. 1982;1:65–78. doi: 10.1002/jcp.1041130412. [DOI] [PubMed] [Google Scholar]
- Lemasters J. J., Sowers A. E. Phosphate dependence and atractyloside inhibition of mitochondrial oxidative phosphorylation. The ADP-ATP carrier is rate-limiting. J Biol Chem. 1979 Feb 25;254(4):1248–1251. [PubMed] [Google Scholar]
- Morgan M. J., Faik P. Carbohydrate metabolism in cultured animal cells. Biosci Rep. 1981 Sep;1(9):669–686. doi: 10.1007/BF01116465. [DOI] [PubMed] [Google Scholar]
- Racker E., Johnson J. H., Blackwell M. T. The role of ATPase in glycolysis of Ehrlich ascites tumor cells. J Biol Chem. 1983 Mar 25;258(6):3702–3705. [PubMed] [Google Scholar]
- Rapoport T. A., Heinrich R., Rapoport S. M. The regulatory principles of glycolysis in erythrocytes in vivo and in vitro. A minimal comprehensive model describing steady states, quasi-steady states and time-dependent processes. Biochem J. 1976 Feb 15;154(2):449–469. doi: 10.1042/bj1540449. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Sachs L. Constitutive uncoupling of pathways of gene expression that control growth and differentiation in myeloid leukemia: a model for the origin and progression of malignancy. Proc Natl Acad Sci U S A. 1980 Oct;77(10):6152–6156. doi: 10.1073/pnas.77.10.6152. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Salter D. W., Baldwin S. A., Lienhard G. E., Weber M. J. Proteins antigenically related to the human erythrocyte glucose transporter in normal and Rous sarcoma virus-transformed chicken embryo fibroblasts. Proc Natl Acad Sci U S A. 1982 Mar;79(5):1540–1544. doi: 10.1073/pnas.79.5.1540. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Salter D. W., Cook J. S. Reversible independent alterations in glucose transport and metabolism in cultured human cells deprived of glucose. J Cell Physiol. 1976 Sep;89(1):143–155. doi: 10.1002/jcp.1040890114. [DOI] [PubMed] [Google Scholar]
- Stanley P. E., Williams S. G. Use of the liquid scintillation spectrometer for determining adenosine triphosphate by the luciferase enzyme. Anal Biochem. 1969 Jun;29(3):381–392. doi: 10.1016/0003-2697(69)90323-6. [DOI] [PubMed] [Google Scholar]
- Tushinski R. J., Oliver I. T., Guilbert L. J., Tynan P. W., Warner J. R., Stanley E. R. Survival of mononuclear phagocytes depends on a lineage-specific growth factor that the differentiated cells selectively destroy. Cell. 1982 Jan;28(1):71–81. doi: 10.1016/0092-8674(82)90376-2. [DOI] [PubMed] [Google Scholar]
- Waterfield M. D., Scrace G. T., Whittle N., Stroobant P., Johnsson A., Wasteson A., Westermark B., Heldin C. H., Huang J. S., Deuel T. F. Platelet-derived growth factor is structurally related to the putative transforming protein p28sis of simian sarcoma virus. Nature. 1983 Jul 7;304(5921):35–39. doi: 10.1038/304035a0. [DOI] [PubMed] [Google Scholar]
- Whetton A. D., Dexter T. M. Effect of haematopoietic cell growth factor on intracellular ATP levels. Nature. 1983 Jun 16;303(5918):629–631. doi: 10.1038/303629a0. [DOI] [PubMed] [Google Scholar]