UROKINASE-TYPE PLASMINOGEN-ACTIVATOR (UPA), A PROTEASE WITH CYTOKINE-LIKE ACTIVITY IN HUMAN HL-60 LEUKEMIC-CELL LINE

HL-60, a cell line originating from a human myeloid leukemia, expresse s urokinase-type plasminogen activator (uPA) on the mRNA level and sec retes the protein into the culture supernatant. Additionally, uPA rece ptors (uPA-R) could be detected in HL-60 on both the mRNA and the prot ein level, whereas the lymphoblastic cell line Raji studied in paralle l was uPA-R negative. The cell lines were further studied in their clo nal growth in methylcellulose under the influence of rhuPA (rhpro-uPA) . The growth of Raji cells was not influenced by rhuPA. Colony and clu ster formation of HL-60 was not reproducibly affected by rhuPA in conc entrations between 1-100 ng/ml. In some experiments however, there wer e higher numbers of colonies in the HL-60 cultures incubated with rhuP A which was due to a cluster-to-colony shift. Furthermore, the HL-60 c olonies in the rhuPA incubated plates always showed morphological alte rations including an adherent basis indicating functional differentiat ion. This assumption was further supported by the observation that the secondary plating efficiency (PE2) of HL-60 cells taken from single c olonies of uPA-incubated plates decreased significantly when compared with PE2 of cells from colonies grown without the presence of uPA. In conclusion, the intact uPA molecule functions like an autocrine cytoki ne for a human leukemic cell line, which in addition to its effects in tumor invasion makes it an interesting target molecule for further st udies on tumor suppression.