Autocrine and possible intracrine regulation of HL-60 cell proliferation by macrophage colony-stimulating factor

The abnormal expression of macrophage colony stimulating factor (M-CSF) iso forms, i.e. membrane bound M-CSF (m-M-CSF) and intracellular M-CSF (c-M-CSF ), and their receptor were reported in some leukemia and tumor cells. Furth ermore, the nuclear localization of them may be related to poor prognosis a nd metastasis, while the mechanism is uncertain. We previously reported tha t m-M-CSF and its receptor played auto-juxtacrine and adhesion molecule rol e in human leukemia cell line J6-1. In this paper, we show that HL-60 cells highly express M-CSF and its receptor. The localization of positive reacti ons was mainly in cytoplasma and nuclear in HL-60 cells. In cytoplasma and nuclear, three isoforms of M-CSF were found with molecular weight (MW) of 2 0, 16 and 14 kDa, while one type of m-CSF receptor (M-CSFR) was discovered with MW of 120 kDa. Immunoprecipitation assay showed that these ligands. co uld exist separately or binding with their receptor. Monoclonal antibody (M cAb) against M-CSF and anti-sense oligodeoxynucleotides (ASON) blocking M-C SF expression inhibited the proliferation of HL-60 cells. McAb and ASON reg ulated the expression of cyclin D1/E, CDK2/4 and p16. Simultaneous administ ration of both McAb and ASON inhibited the proliferation of HL-60 cells and modulate the expression of cyclins at greater degrees. Our results suggest ed an autocrine and possible an intracrine loop of M-CSF/M-CSFR in HL-60 ce lls. (C) 2001 Elsevier Science Ltd. All rights reserved.