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

Journal Article · Wed Aug 01 04:00:00 EDT 1990 · Proceedings of the National Academy of Sciences of the United States of America; (USA)

DOI:https://doi.org/10.1073/pnas.87.15.5613· OSTI ID:6214283

Pierce, J H; Di Marco, E; Lombardi, D; Ruggiero, M; Di Fiore, P P; Aaronson, S A ^[1]; Cox, G W; Varesio, L ^[2]; Wang, Ling Mei; Choudhury, G G; Sakaguchi, A Y ^[3]

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1. National Cancer Institute, Bethesda, MD (USA)
2. National Cancer Institute-Frederick Cancer Research Facility, MD (USA)
3. Univ. of Texas Health Science Center, San Antonio (USA)

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) 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.

• OSTI ID: 6214283
• Journal Information: Proceedings of the National Academy of Sciences of the United States of America; (USA), Journal Name: Proceedings of the National Academy of Sciences of the United States of America; (USA) Vol. 87:15; ISSN PNASA; ISSN 0027-8424
• Country of Publication: United States
• Language: English

Related Subjects

550201* -- Biochemistry-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
ANIMAL CELLS
ANTIGENS
BETA DECAY RADIOISOTOPES
BIOLOGICAL MATERIALS
BLOOD
BLOOD CELLS
BODY FLUIDS
CELL DIFFERENTIATION
CELL PROLIFERATION
CONNECTIVE TISSUE CELLS
DAYS LIVING RADIOISOTOPES
DNA
ELECTRON CAPTURE RADIOISOTOPES
GENE REGULATION
GENES
GROWTH FACTORS
INFLAMMATION
INTERMEDIATE MASS NUCLEI
IODINE 125
IODINE ISOTOPES
ISOTOPE APPLICATIONS
ISOTOPES
LEUKOCYTES
LYMPHOKINES
MACROPHAGES
MATERIALS
MEMBRANE PROTEINS
MITOGENS
MONOCYTES
MORPHOLOGICAL CHANGES
NUCLEI
NUCLEIC ACIDS
ODD-EVEN NUCLEI
ONCOGENES
ORGANIC COMPOUNDS
PATHOLOGICAL CHANGES
PHAGOCYTES
PROTEINS
RADIOISOTOPES
RADIORECEPTOR ASSAY
RECEPTORS
RECOMBINANT DNA
SOMATIC CELLS
SYMPTOMS
TRACER TECHNIQUES