Abstract
Because IL-3-dependent multipotential FDCP-Mix cells expressing human colony-stimulating factor-1 (CSF-1) receptor did not proliferate in response to soluble CSF-1, we investigated whether their proliferation would be induced in co-culture with adherent cells expressing the membrane form of CSF-1 (MemCSF-1). FDCP-Mix cells with high CSF-1R expression (NAF21 cells) were placed on stromal MS-5 cells or STO fibroblasts expressing MemCSF-1 (2M-1 cells and STO-M2 cells, respectively), in absence of IL-3. NAF21 cells bound significantly to 2M-1 cells as compared to control FDCP-Mix cells. Adhesion of NAF21 cells was inhibited by anti-huCSF-1 antibodies, as well as anti-huCSF-1R antibodies. Interestingly, NAF21 cells proliferated on both 2M-1 and STO-M2 cells but with very different kinetics. Moreover, NAF21 cell proliferation was also supported by glutaraldehyde-fixed 2M-1 cells or highly concentrated MS-5 cell culture supernatant, but not by CSF-1 coated on culture dishes. These results strongly suggest that MemCSF-1/CSF-1R interaction mediates a specific adhesion of NAF21 cells to stromal cells and allows stimulation of hematopoietic cells by stromal cell-derived factors expressed in a membrane-bound form or concentrated within the extracellular matrix. Thus, cytokine receptors deficient in mitogenic signalling may nevertheless have a regulatory role in hematopoietic progenitor cell proliferation by acting as adhesion molecules.
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Acknowledgements
This work was supported by grants from Association pour la Recherche sur le Cancer, Fondation contre la Leucémie, Ligue Nationale contre le Cancer and CNRS. VR was a recipient of a fellowship from the Ministère de la Recherche et de I'Enseignement Supérieur and IT was supported by a fellowship from ARC.
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Tsuboi, I., Revol, V., Blanchet, J. et al. Role of the membrane form of human colony-stimulating factor-1 (CSF-1) in proliferation of multipotent hematopoietic FDCP-Mix cells expressing human CSF-1 receptor. Leukemia 14, 1460–1466 (2000). https://doi.org/10.1038/sj.leu.2401847
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DOI: https://doi.org/10.1038/sj.leu.2401847
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