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. 1994 Jan;69(1):152–156. doi: 10.1038/bjc.1994.25

Pancreatic trypsinogen and cathepsin B in human pancreatic carcinomas and associated metastatic lesions.

T Ohta 1, T Terada 1, T Nagakawa 1, H Tajima 1, H Itoh 1, L Fonseca 1, I Miyazaki 1
PMCID: PMC1968761  PMID: 8286198

Abstract

Expression of pancreatic trypsinogen and cathepsin B in 23 surgically resected pancreatic ductal adenocarcinomas was evaluated immunohistochemically, using a monoclonal antibody against human pancreatic trypsinogen and a polyclonal antibody against human cathepsin B. Fifteen of 20 invasive tubular adenocarcinomas (75%) expressed pancreatic trypsinogen in a coarse granular pattern located in the supranuclear cytoplasm of the carcinoma cells. In addition, metastatic lesions, including those in peripancreatic lymph nodes and neural plexuses, expressed pancreatic trypsinogen. In contrast, three intraductal (non-invasive) papillary adenocarcinomas did not express pancreatic trypsinogen. Cathepsin B expression was recognised in 14 of 20 invasive tubular adenocarcinomas (70%) in a fine granular pattern located diffusely in the cytoplasm of the carcinoma cells, while none of the three intraductal papillary adenocarcinomas had detectable cathepsin B. These findings suggest that pancreatic invasive ductal adenocarcinomas express pancreatic trypsinogen and cathepsin B immunoreactive peptides, raising the possibility that pancreatic trypsinogen and cathepsin B may act independently of each other in the process of carcinoma invasion and metastasis, like other different classes of proteases involved in the proteolytic modification of the matrix barrier.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Bansal R., Ahmad N., Kidwai J. R. In vitro conversion of proinsulin to insulin by cathepsin B in isolated islets and its inhibition by cathepsin B antibodies. Acta Diabetol Lat. 1980 Jul-Dec;17(3-4):255–266. doi: 10.1007/BF02581326. [DOI] [PubMed] [Google Scholar]
  2. Cavanaugh P. G., Sloane B. F., Bajkowski A. S., Gasic G. J., Gasic T. B., Honn K. V. Involvement of a cathepsin B-like cysteine proteinase in platelet aggregation induced by tumor cells and their shed membrane vesicles. Clin Exp Metastasis. 1983 Oct-Dec;1(4):297–307. doi: 10.1007/BF00121192. [DOI] [PubMed] [Google Scholar]
  3. Colomb E., Figarella C., Guy O. The two human trypsinogens. Evidence of complex formation with basic pancreatic trypsin inhibitor-proteolytic activity. Biochim Biophys Acta. 1979 Oct 11;570(2):397–405. doi: 10.1016/0005-2744(79)90159-1. [DOI] [PubMed] [Google Scholar]
  4. Conley C. R., Scheithauer B. W., van Heerden J. A., Weiland L. H. Diffuse intraductal papillary adenocarcinoma of the pancreas. Ann Surg. 1987 Mar;205(3):246–249. doi: 10.1097/00000658-198703000-00005. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Cubilla A., Fitzgerald P. J. Pancreas cancer. I. Duct adenocarcinoma. A clinical-pathologic study of 380 patients. Pathol Annu. 1978;13(Pt 1):241–289. [PubMed] [Google Scholar]
  6. Erdel M., Trefz G., Spiess E., Habermaas S., Spring H., Lah T., Ebert W. Localization of cathepsin B in two human lung cancer cell lines. J Histochem Cytochem. 1990 Sep;38(9):1313–1321. doi: 10.1177/38.9.2201737. [DOI] [PubMed] [Google Scholar]
  7. GREENBAUM L. M., HIRSHKOWITZ A., SHOICHET I. The activation of trypsinogen by cathepsin B. J Biol Chem. 1959 Nov;234:2885–2890. [PubMed] [Google Scholar]
  8. Hadorn B., Hess J., Troesch V., Verhaage W., Götze H., Bender S. W. Role of bile acids in the activation of trypsinogen by enterokinase: disturbance of trypsinogen activation in patients with intrahepatic biliary atresia. Gastroenterology. 1974 Apr;66(4):548–555. [PubMed] [Google Scholar]
  9. Halila H., Lehtovirta P., Stenman U. H. Tumour-associated trypsin inhibitor (TATI) in ovarian cancer. Br J Cancer. 1988 Mar;57(3):304–307. doi: 10.1038/bjc.1988.67. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Huhtala M. L., Pesonen K., Kalkkinen N., Stenman U. H. Purification and characterization of a tumor-associated trypsin inhibitor from the urine of a patient with ovarian cancer. J Biol Chem. 1982 Nov 25;257(22):13713–13716. [PubMed] [Google Scholar]
  11. Koivunen E., Huhtala M. L., Stenman U. H. Human ovarian tumor-associated trypsin. Its purification and characterization from mucinous cyst fluid and identification as an activator of pro-urokinase. J Biol Chem. 1989 Aug 25;264(24):14095–14099. [PubMed] [Google Scholar]
  12. Koivunen E., Ristimäki A., Itkonen O., Osman S., Vuento M., Stenman U. H. Tumor-associated trypsin participates in cancer cell-mediated degradation of extracellular matrix. Cancer Res. 1991 Apr 15;51(8):2107–2112. [PubMed] [Google Scholar]
  13. Koivunen E., Saksela O., Itkonen O., Osman S., Huhtala M. L., Stenman U. H. Human colon carcinoma, fibrosarcoma and leukemia cell lines produce tumor-associated trypsinogen. Int J Cancer. 1991 Feb 20;47(4):592–596. doi: 10.1002/ijc.2910470419. [DOI] [PubMed] [Google Scholar]
  14. Köppel P., Baici A., Keist R., Matzku S., Keller R. Cathepsin B-like proteinase as a marker for metastatic tumor cell variants. Exp Cell Biol. 1984;52(5):293–299. doi: 10.1159/000163273. [DOI] [PubMed] [Google Scholar]
  15. Marks W. H., Ohlsson K., Polling A. Immunocytochemical distribution of trypsinogen and pancreatic secretory trypsin inhibitor in normal and neoplastic tissues in man. Scand J Gastroenterol. 1984 Jul;19(5):673–676. [PubMed] [Google Scholar]
  16. McCutcheon A. D. A fresh approach to the pathogenesis of pancreatitis. Gut. 1968 Jun;9(3):296–310. doi: 10.1136/gut.9.3.296. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Miszczuk-Jamska B., Merten M., Guy-Crotte O., Amouric M., Clemente F., Schoumacher R. A., Figarella C. Characterization of trypsinogens 1 and 2 in two human pancreatic adenocarcinoma cell lines; CFPAC-1 and CAPAN-1. FEBS Lett. 1991 Dec 9;294(3):175–178. doi: 10.1016/0014-5793(91)80662-m. [DOI] [PubMed] [Google Scholar]
  18. Morohoshi T., Kanda M., Asanuma K., Klöppel G. Intraductal papillary neoplasms of the pancreas. A clinicopathologic study of six patients. Cancer. 1989 Sep 15;64(6):1329–1335. doi: 10.1002/1097-0142(19890915)64:6<1329::aid-cncr2820640627>3.0.co;2-s. [DOI] [PubMed] [Google Scholar]
  19. Mort J. S., Recklies A. D. Interrelationship of active and latent secreted human cathepsin B precursors. Biochem J. 1986 Jan 1;233(1):57–63. doi: 10.1042/bj2330057. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Pietras R. J., Roberts J. A. Cathepsin B-like enzymes. Subcellular distribution and properties in neoplastic and control cells from human ectocervix. J Biol Chem. 1981 Aug 25;256(16):8536–8544. [PubMed] [Google Scholar]
  21. Pour P. M. Induction of unusual pancreatic neoplasms, with morphologic similarity to human tumors, and evidence for their ductal/ductular cell origin. Cancer. 1985 May 15;55(10):2411–2416. doi: 10.1002/1097-0142(19850515)55:10<2411::aid-cncr2820551019>3.0.co;2-1. [DOI] [PubMed] [Google Scholar]
  22. Pour P. M. Mechanism of pseudoductular (tubular) formation during pancreatic carcinogenesis in the hamster model. An electron-microscopic and immunohistochemical study. Am J Pathol. 1988 Feb;130(2):335–344. [PMC free article] [PubMed] [Google Scholar]
  23. Recklies A. D., Tiltman K. J., Stoker T. A., Poole A. R. Secretion of proteinases from malignant and nonmalignant human breast tissue. Cancer Res. 1980 Mar;40(3):550–556. [PubMed] [Google Scholar]
  24. Rickaert F., Cremer M., Devière J., Tavares L., Lambilliotte J. P., Schröder S., Wurbs D., Klöppel G. Intraductal mucin-hypersecreting neoplasms of the pancreas. A clinicopathologic study of eight patients. Gastroenterology. 1991 Aug;101(2):512–519. doi: 10.1016/0016-5085(91)90032-g. [DOI] [PubMed] [Google Scholar]
  25. Rozhin J., Robinson D., Stevens M. A., Lah T. T., Honn K. V., Ryan R. E., Sloane B. F. Properties of a plasma membrane-associated cathepsin B-like cysteine proteinase in metastatic B16 melanoma variants. Cancer Res. 1987 Dec 15;47(24 Pt 1):6620–6628. [PubMed] [Google Scholar]
  26. Sloane B. F. Cathepsin B and cystatins: evidence for a role in cancer progression. Semin Cancer Biol. 1990 Apr;1(2):137–152. [PubMed] [Google Scholar]
  27. Sloane B. F., Rozhin J., Johnson K., Taylor H., Crissman J. D., Honn K. V. Cathepsin B: association with plasma membrane in metastatic tumors. Proc Natl Acad Sci U S A. 1986 Apr;83(8):2483–2487. doi: 10.1073/pnas.83.8.2483. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Stenman U. H., Koivunen E., Vuento M. Characterization of a tumor-associated serine protease. Biol Chem Hoppe Seyler. 1988 May;369 (Suppl):9–14. [PubMed] [Google Scholar]
  29. Talbot R. W., Grant D. A., Hermon-Taylor J. Displacement of endogenous enterokinase into portal venous blood and bile following luminal perfusion of proximal small intestine in guinea pigs. Dig Dis Sci. 1984 Nov;29(11):1009–1014. doi: 10.1007/BF01311252. [DOI] [PubMed] [Google Scholar]
  30. Tryggvason K., Höyhtyä M., Salo T. Proteolytic degradation of extracellular matrix in tumor invasion. Biochim Biophys Acta. 1987 Nov 25;907(3):191–217. doi: 10.1016/0304-419x(87)90006-0. [DOI] [PubMed] [Google Scholar]
  31. Weiss R. E., Liu B. C., Ahlering T., Dubeau L., Droller M. J. Mechanisms of human bladder tumor invasion: role of protease cathepsin B. J Urol. 1990 Sep;144(3):798–804. doi: 10.1016/s0022-5347(17)39595-2. [DOI] [PubMed] [Google Scholar]

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