Enhanced plasminogen activator production of Syrian hamster embryo cells transformed by chemicals or the c-Ha-ras oncogene: type of plasminogen activators involved and their contribution to the transformed phenotype.
The plasminogen activator (PA) activity produced by Syrian hamster embryo (SHE) cells in different stages of neoplastic conversion was analysed. PA activity was characterized immunologically and by SDS-PAGE. Normal SHE cells had a very low PA activity. Although activity of either the tissue type of PA (t-PA) or the urokinase type (u-PA) or both were found to be increased in most immortal or transformed SHE cells, there was no correlation between enhanced production of a particular PA type and the development of the immortal or transformed phenotype. However, within a group of cell lines clonally derived from a culture of immortal cells, a positive correlation was found between extracellular t-PA, but not u-PA, activity and cellular growth rate. For the Syrian hamster PA species, crossreacting with anti-human u-PA, a mol. wt of 39 kd was observed. For the Syrian hamster PA species, crossreacting with anti-human t-PA, multiple species were found with mol. wts of 98, 72 and 59 kd respectively. Evidence was obtained that the 72-kd species represents the intact enzyme, the 59-kd species a partial digestion product thereof and the 98 kd species, which often appears as a doublet, a complex of either of these species with an inhibitor, likely to be secreted by the same cells. Finally, our data suggest a novel mechanism for the enhancement of t-PA activity of transformed cells, namely by a decrease in the effective extracellular amount of putative inhibitor.
de Kok
A J
AJ
Department of Radiation Genetics and Chemical Mutagenesis, Sylvius Laboratories, State University of Leiden, The Netherlands.
Sips
H
H
Chang
G T
GT
Verheijen
J H
JH
D000818:Animals; D000906:Antibodies; D001564:Benzo(a)pyrene / Q000494:pharmacology; D002273:Carcinogens / Q000494:pharmacology*; D002460:Cell Line; D002471:Cell Transformation, Neoplastic; D006224:Cricetinae; D004622:Embryo, Mammalian; D004792:Enzyme Precursors / Q000096:biosynthesis*; D005038:Ethylnitrosourea / Q000494:pharmacology; D011905:Genes, ras; D006801:Humans; D007328:Insulin / Q000494:pharmacology; D007531:Isoflurophate / Q000494:pharmacology; D008647:Mesocricetus; D010641:Phenotype; D010960:Plasminogen Activators / Q000096:biosynthesis*; D010959:Tissue Plasminogen Activator / Q000096:biosynthesis*; D014568:Urokinase-Type Plasminogen Activator / Q000096:biosynthesis*
D000906:Antibodies; D002273:Carcinogens; D004792:Enzyme Precursors; D007328:Insulin; D007531:Isoflurophate; D001564:Benzo(a)pyrene; D010960:Plasminogen Activators; D010959:Tissue Plasminogen Activator; D014568:Urokinase-Type Plasminogen Activator; D005038:Ethylnitrosourea