[Protease inhibitors as tumor-associated growth factors]

Two apparent endothelial cell growth factors were isolated and characterized from serum free cell culture medium of hepatoma cells by McKeehan et al. The factors were identified as proteinase inhibitors with known primary structure. They are the pancreatic secretory trypsin inhibitor (HPSTI) and the double headed inhibitor HI-30, the inhibitory active part of the inter-alpha-trypsin inhibitor complex. We were able to isolate acid resistant inhibitory active material from serum free culture medium of 4 out of 11 tumor cell lines, which we have analyzed. The cell lines were not derived from liver cells. The inhibitory active material was identified as the inhibitor HI-30 by N-terminal amino acid sequence analysis. The results indicate that HI-30 is a real growth factor, since it is expressed as well in tumor cells which are not derived from liver cells.