Skip to main content
NCBI home page
Gut logoLink to Gut
. 1987 Jul;28(7):816–821. doi: 10.1136/gut.28.7.816

Plasminogen activators in experimental colorectal neoplasia: a role in the adenoma-carcinoma sequence?

J S Gelister 1, M R Lewin 1, H E Driver 1, F Savage 1, M Mahmoud 1, P J Gaffney 1, P B Boulos 1
PMCID: PMC1433066  PMID: 3115868

Abstract

An important step in the transition from adenomatous polyp to invasive carcinoma is the degradation of the epithelial basement membrane. By the generation of plasmin, plasminogen activators may play an important role in regulating the extracellular protease activity required for this event to occur. The production of biofunctional urokinase and of tissue plasminogen activator was therefore investigated in the dimethylhydrazine induced rat model of colorectal neoplasia. Both adenomatous polyps (p values less than 0.001) and colorectal carcinomas (p values less than 0.001) were demonstrated to produce a significant excess of both urokinase and tissue plasminogen activator when compared with macroscopically normal colon. There was, however, no increased production of either enzyme by macroscopically normal preneoplastic colon when compared with control colon. This enhanced capacity of colorectal tumours to produce plasminogen activators and generate plasmin is thus a feature of both the premalignant as well as the malignant phenotype. These enzymes may contribute to the malignant potential of adenomatous polyps and to the invasive capacity of established carcinomas.

Full text

PDF
816

Selected References

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

  1. Corasanti J. G., Hobika G. H., Markus G. Interference with dimethylhydrazine induction of colon tumors in mice by epsilon-aminocaproic acid. Science. 1982 May 28;216(4549):1020–1021. doi: 10.1126/science.6805074. [DOI] [PubMed] [Google Scholar]
  2. Day D. W. The adenoma-carcinoma sequence. Scand J Gastroenterol Suppl. 1984;104:99–107. [PubMed] [Google Scholar]
  3. Duffy M. J., O'Grady P. Plasminogen activator and cancer. Eur J Cancer Clin Oncol. 1984 May;20(5):577–582. doi: 10.1016/0277-5379(84)90001-4. [DOI] [PubMed] [Google Scholar]
  4. Durdey P., Cooper J. C., Switala S., King R. F., Williams N. S. The role of peptidases in cancer of the rectum and sigmoid colon. Br J Surg. 1985 May;72(5):378–381. doi: 10.1002/bjs.1800720515. [DOI] [PubMed] [Google Scholar]
  5. Gelister J. S., Mahmoud M., Lewin M. R., Gaffney P. J., Boulos P. B. Plasminogen activators in human colorectal neoplasia. Br Med J (Clin Res Ed) 1986 Sep 20;293(6549):728–731. doi: 10.1136/bmj.293.6549.728. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Green L. J., Rumsby P. C., Roscoe J. P. An increase in plasminogen activator mRNA occurs at an early stage in ethylnitrosourea-induced transformation of rat brain cells. Carcinogenesis. 1986 Mar;7(3):477–480. doi: 10.1093/carcin/7.3.477. [DOI] [PubMed] [Google Scholar]
  7. Gross J. L., Krupp M. N., Rifkin D. B., Lane M. D. Down-regulation of epidermal growth factor receptor correlates with plasminogen activator activity in human A431 epidermoid carcinoma cells. Proc Natl Acad Sci U S A. 1983 Apr;80(8):2276–2280. doi: 10.1073/pnas.80.8.2276. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Hinuma S., Honda S., Tsukamoto K., Sugamura K., Hinuma Y. Production of plasminogen activators by human T-cell leukaemia virus-transformed human T cell lines. Br J Cancer. 1985 Jun;51(6):753–759. doi: 10.1038/bjc.1985.118. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Kjaeldgaard A., Larsson B., Astedt B. Immunological comparison between human and rat plasminogen activators in blood and the vessel wall. J Clin Pathol. 1984 Oct;37(10):1153–1156. doi: 10.1136/jcp.37.10.1153. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. MORSON B. C. Precancerous lesions of the colon and rectum. Classification and controversial issues. JAMA. 1962 Feb 3;179:316–321. doi: 10.1001/jama.1962.03050050006002. [DOI] [PubMed] [Google Scholar]
  11. Madara J. L., Harte P., Deasy J., Ross D., Lahey S., Steele G., Jr Evidence for an adenoma-carcinoma sequence in dimethylhydrazine-induced neoplasms of rat intestinal epithelium. Am J Pathol. 1983 Feb;110(2):230–235. [PMC free article] [PubMed] [Google Scholar]
  12. Markus G., Camiolo S. M., Kohga S., Madeja J. M., Mittelman A. Plasminogen activator secretion of human tumors in short-term organ culture, including a comparison of primary and metastatic colon tumors. Cancer Res. 1983 Nov;43(11):5517–5525. [PubMed] [Google Scholar]
  13. Matsuo O., Rijken D. C., Collen D. Comparison of the relative fibrinogenolytic, fibrinolytic and thrombolytic properties of tissue plasminogen activator and urokinase in vitro. Thromb Haemost. 1981 Jun 30;45(3):225–229. [PubMed] [Google Scholar]
  14. Muto T., Bussey H. J., Morson B. C. The evolution of cancer of the colon and rectum. Cancer. 1975 Dec;36(6):2251–2270. doi: 10.1002/cncr.2820360944. [DOI] [PubMed] [Google Scholar]
  15. O'Grady P., Lijnen H. R., Duffy M. J. Multiple forms of plasminogen activator in human breast tumors. Cancer Res. 1985 Dec;45(12 Pt 1):6216–6218. [PubMed] [Google Scholar]
  16. O'Grady R. L., Upfold L. I., Stephens R. W. Rat mammary carcinoma cells secrete active collagenase and activate latent enzyme in the stroma via plasminogen activator. Int J Cancer. 1981 Oct 15;28(4):509–515. doi: 10.1002/ijc.2910280418. [DOI] [PubMed] [Google Scholar]
  17. Tissot J. D., Hauert J., Bachmann F. Characterization of plasminogen activators from normal human breast and colon and from breast and colon carcinomas. Int J Cancer. 1984 Sep 15;34(3):295–302. doi: 10.1002/ijc.2910340302. [DOI] [PubMed] [Google Scholar]
  18. Verheijen J. H., Mullaart E., Chang G. T., Kluft C., Wijngaards G. A simple, sensitive spectrophotometric assay for extrinsic (tissue-type) plasminogen activator applicable to measurements in plasma. Thromb Haemost. 1982 Dec 27;48(3):266–269. [PubMed] [Google Scholar]

Articles from Gut are provided here courtesy of BMJ Publishing Group

RESOURCES