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

Jacalyn H. Pierce, Eddi D I Marco, George W. Cox, Daniela Lombardi, Marco Ruggiero, Luigi Varesio, Ling Mei Wang, G. Ghosh Choudhury, Alan Y. Sakaguchi, Pier Paolo Di Fiore, Stuart A. Aaronson

Research output: Contribution to journalArticlepeer-review

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-/ms 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-/ms[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
Pages (from-to)5613-5617
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume87
Issue number15
Publication statusPublished - 1990

ASJC Scopus subject areas

  • Genetics
  • General

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