Production of a serine-protease with macrophage migration-inhibitory factor activity by virus-transformed cells and human tumor cell lines.
BALB/c mouse 3T3 cells transformed by simian virus 40 (SV3T3), baby hamster kidney cells transformed by polyoma virus or Rous sarcoma virus, and a range of neoplastic human cell lines release material that inhibits the migration of macrophages and lymphocytes. Similar migration-inhibitory factor (MIF) activity was not detected in supernatants from cultures of untransformed 3T3 or baby hamster kidney cells and a variety of human diploid cell strains. Physico-chemical characterization of the MIF produced by SV3T3 and HeLa cells revealed substantial similarities with the MIF produced by mitogen-activated human peripheral lymphocytes. MIF released by tumor cells is inhibited by pancreatic and soybean trypsin inhibitors and by diisopropylfluorophosphate, indicating that it is a serine-protease. Comparison of MIF produced by SV3T3 cells with a serine-protease plasminogen activator released by the same cells indicated that the latter is more heat labile and has a more heterogenous elution profile after chromatography on Sephadex G-75. The possible role of MIF in causing proteolytic modification of the surface properties of tumor cells and in altering cell-mediated immune responses to neoplastic cells is discussed.
D000818:Animals; D001358:Avian Sarcoma Viruses; D002460:Cell Line; D002464:Cell Migration Inhibition; D002471:Cell Transformation, Neoplastic; D002474:Cell-Free System; D002918:Chymotrypsin / Q000494:pharmacology; D006224:Cricetinae; D010450:Endopeptidases / Q000096:biosynthesis*; D006367:HeLa Cells / Q000378:metabolism; D006358:Hot Temperature; D006801:Humans; D007531:Isoflurophate / Q000494:pharmacology; D008214:Lymphocytes; D008263:Macrophage Migration-Inhibitory Factors / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D008264:Macrophages; D051379:Mice; D008807:Mice, Inbred BALB C; D009369:Neoplasms / Q000378:metabolism*; D011120:Polyomavirus; D012694:Serine; D013539:Simian virus 40; D014361:Trypsin Inhibitors / Q000494:pharmacology
D008263:Macrophage Migration-Inhibitory Factors; D014361:Trypsin Inhibitors; D007531:Isoflurophate; D012694:Serine; D010450:Endopeptidases; D002918:Chymotrypsin