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Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1991 Jul 15;88(14):6239–6243. doi: 10.1073/pnas.88.14.6239

Direct proliferative actions of stem cell factor on murine bone marrow cells in vitro: effects of combination with colony-stimulating factors.

D Metcalf 1, N A Nicola 1
PMCID: PMC52058  PMID: 1712485

Abstract

Stem cell factor (SCF), the ligand for the c-kit protooncogene product, was able to stimulate blast cell and granulocytic colony formation by precursors from normal murine bone marrow. The blast cell colonies contained a high content of progenitor cells able to form macrophage and/or granulocyte colonies. Clone transfer studies, the secondary culture of colony cells, and the culture of populations freed of accessory cells all indicated a direct proliferative action of SCF. SCF receptors were present in high numbers on blast cells and in lower numbers on immature granulocytic, monocytic, and eosinophilic cells. Combination of SCF with granulocyte, granulocyte-macrophage, or multipotential colony-stimulating factors, but not macrophage colony-stimulating factor, resulted in enhancement of colony size. Granulocyte colony-stimulating factor enhanced cell proliferation initiated by SCF, but not vice-versa, and resulted in a 10-fold increase in colony cell numbers and a 7-fold increase in progenitor cells in blast colonies. No evidence was obtained that SCF, alone or in combination with granulocyte colony-stimulating factor, could stimulate self-generation by blast colony-forming cells.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Anderson D. M., Lyman S. D., Baird A., Wignall J. M., Eisenman J., Rauch C., March C. J., Boswell H. S., Gimpel S. D., Cosman D. Molecular cloning of mast cell growth factor, a hematopoietin that is active in both membrane bound and soluble forms. Cell. 1990 Oct 5;63(1):235–243. doi: 10.1016/0092-8674(90)90304-w. [DOI] [PubMed] [Google Scholar]
  2. Chabot B., Stephenson D. A., Chapman V. M., Besmer P., Bernstein A. The proto-oncogene c-kit encoding a transmembrane tyrosine kinase receptor maps to the mouse W locus. Nature. 1988 Sep 1;335(6185):88–89. doi: 10.1038/335088a0. [DOI] [PubMed] [Google Scholar]
  3. Cynshi O., Satoh K., Shimonaka Y., Hattori K., Nomura H., Imai N., Hirashima K. Reduced response to granulocyte colony-stimulating factor in W/Wv and Sl/Sld mice. Leukemia. 1991 Jan;5(1):75–77. [PubMed] [Google Scholar]
  4. Geissler E. N., Ryan M. A., Housman D. E. The dominant-white spotting (W) locus of the mouse encodes the c-kit proto-oncogene. Cell. 1988 Oct 7;55(1):185–192. doi: 10.1016/0092-8674(88)90020-7. [DOI] [PubMed] [Google Scholar]
  5. Hilton D. J., Nicola N. A., Metcalf D. Specific binding of murine leukemia inhibitory factor to normal and leukemic monocytic cells. Proc Natl Acad Sci U S A. 1988 Aug;85(16):5971–5975. doi: 10.1073/pnas.85.16.5971. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Martin F. H., Suggs S. V., Langley K. E., Lu H. S., Ting J., Okino K. H., Morris C. F., McNiece I. K., Jacobsen F. W., Mendiaz E. A. Primary structure and functional expression of rat and human stem cell factor DNAs. Cell. 1990 Oct 5;63(1):203–211. doi: 10.1016/0092-8674(90)90301-t. [DOI] [PubMed] [Google Scholar]
  7. Metcalf D., Merchav S. Effects of GM-CSF deprivation on precursors of granulocytes and macrophages. J Cell Physiol. 1982 Sep;112(3):411–418. doi: 10.1002/jcp.1041120315. [DOI] [PubMed] [Google Scholar]
  8. Morstyn G., Campbell L., Souza L. M., Alton N. K., Keech J., Green M., Sheridan W., Metcalf D., Fox R. Effect of granulocyte colony stimulating factor on neutropenia induced by cytotoxic chemotherapy. Lancet. 1988 Mar 26;1(8587):667–672. doi: 10.1016/s0140-6736(88)91475-4. [DOI] [PubMed] [Google Scholar]
  9. Spangrude G. J., Johnson G. R. Resting and activated subsets of mouse multipotent hematopoietic stem cells. Proc Natl Acad Sci U S A. 1990 Oct;87(19):7433–7437. doi: 10.1073/pnas.87.19.7433. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Tamura M., Hattori K., Nomura H., Oheda M., Kubota N., Imazeki I., Ono M., Ueyama Y., Nagata S., Shirafuji N. Induction of neutrophilic granulocytosis in mice by administration of purified human native granulocyte colony-stimulating factor (G-CSF). Biochem Biophys Res Commun. 1987 Jan 30;142(2):454–460. doi: 10.1016/0006-291x(87)90296-8. [DOI] [PubMed] [Google Scholar]
  11. Zsebo K. M., Wypych J., McNiece I. K., Lu H. S., Smith K. A., Karkare S. B., Sachdev R. K., Yuschenkoff V. N., Birkett N. C., Williams L. R. Identification, purification, and biological characterization of hematopoietic stem cell factor from buffalo rat liver--conditioned medium. Cell. 1990 Oct 5;63(1):195–201. doi: 10.1016/0092-8674(90)90300-4. [DOI] [PubMed] [Google Scholar]

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