title: Human colon carcinoma, fibrosarcoma and leukemia cell lines produce tumor-associated trypsinogen.
abstract: Previous studies have indicated that cyst fluid of ovarian tumors contains 2 trypsinogen isoenzymes, called tumor-associated trypsinogen-I (TAT-I) and trypsinogen-2 (TAT-2), the levels of which correlate with the degree of malignancy of the tumors. In addition, these cyst fluids contain large amounts of tumor-associated trypsin inhibitor (TATI), which is also expressed in many other human tumors. In the present study we examined the production of TAT-I, TAT-2 and TATI in 9 established tumor-cell lines. TAT-2 was produced by 5 cell lines. Its concentration in the conditioned medium of COLO 205 colon adenocarcinoma cells, K-562 erythroleukemia cells and fibrosarcoma cell lines HT 1080, 8387 and A 9733 was 460 micrograms/l, 9.8 micrograms/l, 21 micrograms/l, 8.8 micrograms/l and 0.24 micrograms/l, respectively. TAT-I was detectable in the conditioned medium of COLO 205 and HT 1080 cells at concentrations of 64 micrograms/l and 0.5 micrograms/l, respectively. TATI was detected only in the media of COLO 205 cells at a concentration of 23 micrograms/l. TAT-2 zymogen was purified from the conditioned medium of COLO 205 and HT 1080 cells by immunoaffinity chromatography. According to its aminoterminal amino acid sequence, a molecular mass of 28 kDa by SDS-PAGE, elution pattern in ion-exchange chromatography and ability to be activated by enteropeptidase, the zymogen is identical to that previously isolated from cyst fluid of ovarian tumors. In addition, we found that TAT-2 secretion could be down-regulated by dexamethasone in HT 1080 cells but not in COLO 205 cells. The abundant production of TAT-2 isoenzyme in different cancer cell lines suggests that it could contribute to the increased proteolytic activity of many human tumors.
authors.affiliation: Department of Obstetrics and Gynecology, Helsinki University Central Hospital, Finland.
authors.forename: E
authors.initials: E
authors.lastname: Koivunen
authors.forename: O
authors.initials: O
authors.lastname: Saksela
authors.forename: O
authors.initials: O
authors.lastname: Itkonen
authors.forename: S
authors.initials: S
authors.lastname: Osman
authors.forename: M L
authors.initials: ML
authors.lastname: Huhtala
authors.forename: U H
authors.initials: UH
authors.lastname: Stenman
mesh_terms: D002277:Carcinoma / Q000201:enzymology*; D003110:Colonic Neoplasms / Q000201:enzymology*; D003907:Dexamethasone / Q000494:pharmacology; D005109:Extracellular Matrix / Q000378:metabolism; D005354:Fibrosarcoma / Q000201:enzymology*; D006801:Humans; D007527:Isoenzymes / Q000032:analysis*; D007938:Leukemia / Q000201:enzymology*; D014362:Trypsinogen / Q000096:biosynthesis* / Q000302:isolation & purification / Q000502:physiology; D014407:Tumor Cells, Cultured
chemical_list: D007527:Isoenzymes; D003907:Dexamethasone; D014362:Trypsinogen