title: Macrophage-colony-stimulating factor (CSF-1) induces proliferation, chemotaxis, and reversible monocytic differentiation in myeloid progenitor cells transfected with the human c-fms/CSF-1 receptor cDNA.
abstract: The c-fms protooncogene encodes the receptor for macrophage-colony-stimulating factor (CSF-1). Expression vectors containing either normal or oncogenic point-mutated human c-fms genes were transfected into interleukin 3 (IL-3)-dependent 32D cells in order to determine the effects of CSF-1 signaling in this murine clonal myeloid progenitor cell line. CSF-1 was shown to trigger proliferation in association with monocytic differentiation of the 32D-c-fms cells. Monocytic differentiation was reversible upon removal of CSF-1, implying that CSF-1 was required for maintenance of the monocyte phenotype but was not sufficient to induce an irrevocable commitment to differentiation. Human CSF-1 was also shown to be a potent chemoattractant for 32D-c-fms cells, suggesting that CSF-1 may serve to recruit monocytes from the circulation to tissue sites of inflammation or injury. Although c-fms did not release 32D cells from factor dependence, point-mutated c-fms[S301,F969] (Leu-301----Ser, Tyr-969----Phe) was able to abrogate their IL-3 requirement and induce tumorigenicity. IL-3-independent 32D-c-fms[S301,F969] cells also displayed a mature monocyte phenotype, implying that differentiation did not interfere with progression of these cells to the malignant state. All of these findings demonstrate that a single growth factor receptor can specifically couple with multiple intracellular signaling pathways and play a critical role in modulating cell proliferation, differentiation, and migration.
authors.affiliation: Laboratory of Cellular and Molecular Biology, National Cancer Institute, Bethesda, MD 20892.
authors.forename: J H
authors.initials: JH
authors.lastname: Pierce
authors.forename: E
authors.initials: E
authors.lastname: Di Marco
authors.forename: G W
authors.initials: GW
authors.lastname: Cox
authors.forename: D
authors.initials: D
authors.lastname: Lombardi
authors.forename: M
authors.initials: M
authors.lastname: Ruggiero
authors.forename: L
authors.initials: L
authors.lastname: Varesio
authors.forename: L M
authors.initials: LM
authors.lastname: Wang
authors.forename: G G
authors.initials: GG
authors.lastname: Choudhury
authors.forename: A Y
authors.initials: AY
authors.lastname: Sakaguchi
authors.forename: P P
authors.initials: PP
authors.lastname: Di Fiore
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects*; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D002633:Chemotaxis / Q000187:drug effects*; D003115:Colony-Stimulating Factors / Q000378:metabolism / Q000494:pharmacology*; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000187:drug effects; D006801:Humans; D007377:Interleukin-3 / Q000494:pharmacology; D016173:Macrophage Colony-Stimulating Factor; D009000:Monocytes / Q000166:cytology* / Q000187:drug effects / Q000502:physiology; D009154:Mutation; D011518:Proto-Oncogene Proteins / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D016186:Receptor, Macrophage Colony-Stimulating Factor; D011956:Receptors, Cell Surface / Q000502:physiology*; D014162:Transfection
chemical_list: D003115:Colony-Stimulating Factors; D007377:Interleukin-3; D011518:Proto-Oncogene Proteins; D011956:Receptors, Cell Surface; D016173:Macrophage Colony-Stimulating Factor; D016186:Receptor, Macrophage Colony-Stimulating Factor