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

J. H. Pierce, E. Di Marco, G. W. Cox, D. Lombardi, M. Ruggiero, L. Varesio, L. M. Wang, G. G. Choudhury, A. Y. Sakaguchi, P. P. Di Fiore, S. A. Aaronson

Research output: Contribution to journalArticle

77 Scopus citations

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 32 D-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.

Original languageEnglish (US)
Pages (from-to)5613-5617
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume87
Issue number15
DOIs
StatePublished - Aug 23 1990
Externally publishedYes

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