[Autocrine growth factor produced by a human promyelocytic leukemia cell line]

Recently, a number of novel growth factors have been identified in culture medium conditioned by tumor cell lines. It is tempting to speculate that these growth factors produced by tumor cells could act as very good tumor markers. We have found that the conditioned medium of human promyelocytic leukemia cells (HL-60) stimulated [3H] glucose incorporation into lipids in rat adipocytes. When the conditioned medium was subjected to gel filtration on a Sephadex G-100 column, this activity was eluted in the fraction corresponding to a molecular weight of 10-12 K daltons. The production of this factor was maximal in the early log phase of cell growth and declined with increasing cell density. Differentiation of HL-60 cells to macrophages was also associated with a decrease in the production of this factor. This factor also stimulated [3H] thymidine uptake into DNA and cell proliferation in HL-60 cells themselves. These data suggest the possibility of autocrine growth of HL-60 as a result of this factor. We have subsequently tried to purify this factor. Two liters of serum-free conditioned HL-60 medium were used as a starting material. The material was purified by gel filtration, ion-exchange chromatography and high-performance liquid chromatography. Finally, 1.1 microgram of purified sample was obtained. The degree of purification was 115,613-fold. Growth factors can be very good tumor markers because this is the only tumor marker which has now been clarified to have an important role in tumor growth.