Abstract
Human colon adenocarcinomas and adjacent normal colon tissues were stained immunohistochemically with three different monoclonal antibodies and one preparation of polyclonal antibodies against each of the two plasminogen activators, uPA (urokinase type) and tPA (tissue type). The staining patterns seen with the respective sets of antibodies were identical. In all of 10 cases, staining for uPA in the normal colon tissue was confined to scattered fibroblastlike cells in the lamina propria. Other cells, including epithelial and endothelial cells, were uPA negative. All the tumor infiltrates contained many more uPA-positive cells than the normal tissues, but the staining was confined to fibroblastlike cells and endothelial cells in the tumor stroma, while no staining of the malignant epithelial cells was detected. Analysis for uPA by enzyme-linked immunosorbent assay (ELISA) in four cases showed an average uPA content of 0.15 ng uPA/mg protein in the normal colon tissues and 1.6 ng uPA/mg protein in the tumors. Tissue-type plasminogen activator immunoreactivity was confined to endothelial cells in both the normal colon tissue and in the colon carcinomas. These findings may indicate that colon cancer cells recruit stromal cells to produce uPA involved in degradation of the extracellular matrix during invasive growth.
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- Behrendt N., Rønne E., Ploug M., Petri T., Løber D., Nielsen L. S., Schleuning W. D., Blasi F., Appella E., Danø K. The human receptor for urokinase plasminogen activator. NH2-terminal amino acid sequence and glycosylation variants. J Biol Chem. 1990 Apr 15;265(11):6453–6460. [PubMed] [Google Scholar]
- Blasi F., Vassalli J. D., Danø K. Urokinase-type plasminogen activator: proenzyme, receptor, and inhibitors. J Cell Biol. 1987 Apr;104(4):801–804. doi: 10.1083/jcb.104.4.801. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Bonsall R. W., Hunt S. Characteristics of interactions between surfactants and the human erythrocyte membrane. Biochim Biophys Acta. 1971 Oct 12;249(1):266–280. doi: 10.1016/0005-2736(71)90104-0. [DOI] [PubMed] [Google Scholar]
- Boyd D., Florent G., Chakrabarty S., Brattain D., Brattain M. G. Alterations of the biological characteristics of a colon carcinoma cell line by colon-derived substrata material. Cancer Res. 1988 May 15;48(10):2825–2831. [PubMed] [Google Scholar]
- Boyd D., Florent G., Kim P., Brattain M. Determination of the levels of urokinase and its receptor in human colon carcinoma cell lines. Cancer Res. 1988 Jun 1;48(11):3112–3116. [PubMed] [Google Scholar]
- Burtin P., Chavanel G., André-Bougaran J., Gentile A. The plasmin system in human adenocarcinomas and their metastases. A comparative immunofluorescence study. Int J Cancer. 1987 Feb 15;39(2):170–178. doi: 10.1002/ijc.2910390208. [DOI] [PubMed] [Google Scholar]
- Cajot J. F., Kruithof E. K., Schleuning W. D., Sordat B., Bachmann F. Plasminogen activators, plasminogen activator inhibitors and procoagulant analyzed in twenty human tumor cell lines. Int J Cancer. 1986 Nov 15;38(5):719–727. doi: 10.1002/ijc.2910380516. [DOI] [PubMed] [Google Scholar]
- Danø K., Andreasen P. A., Grøndahl-Hansen J., Kristensen P., Nielsen L. S., Skriver L. Plasminogen activators, tissue degradation, and cancer. Adv Cancer Res. 1985;44:139–266. doi: 10.1016/s0065-230x(08)60028-7. [DOI] [PubMed] [Google Scholar]
- Davies R. L., Rifkin D. B., Tepper R., Miller A., Kucherlapati R. A polypeptide secreted by transformed cells that modulates human plasminogen activator production. Science. 1983 Jul 8;221(4606):171–173. doi: 10.1126/science.6682999. [DOI] [PubMed] [Google Scholar]
- Ellis V., Scully M. F., Kakkar V. V. Plasminogen activation by single-chain urokinase in functional isolation. A kinetic study. J Biol Chem. 1987 Nov 5;262(31):14998–15003. [PubMed] [Google Scholar]
- Ellis V., Scully M. F., Kakkar V. V. Plasminogen activation initiated by single-chain urokinase-type plasminogen activator. Potentiation by U937 monocytes. J Biol Chem. 1989 Feb 5;264(4):2185–2188. [PubMed] [Google Scholar]
- Gelister J. S., Lewin M. R., Driver H. E., Savage F., Mahmoud M., Gaffney P. J., Boulos P. B. Plasminogen activators in experimental colorectal neoplasia: a role in the adenoma-carcinoma sequence? Gut. 1987 Jul;28(7):816–821. doi: 10.1136/gut.28.7.816. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Grøndahl-Hansen J., Agerlin N., Munkholm-Larsen P., Bach F., Nielsen L. S., Dombernowsky P., Danø K. Sensitive and specific enzyme-linked immunosorbent assay for urokinase-type plasminogen activator and its application to plasma from patients with breast cancer. J Lab Clin Med. 1988 Jan;111(1):42–51. [PubMed] [Google Scholar]
- Grøndahl-Hansen J., Kirkeby L. T., Ralfkiaer E., Kristensen P., Lund L. R., Danø K. Urokinase-type plasminogen activator in endothelial cells during acute inflammation of the appendix. Am J Pathol. 1989 Oct;135(4):631–636. [PMC free article] [PubMed] [Google Scholar]
- Grøndahl-Hansen J., Lund L. R., Ralfkiaer E., Ottevanger V., Danø K. Urokinase- and tissue-type plasminogen activators in keratinocytes during wound reepithelialization in vivo. J Invest Dermatol. 1988 Jun;90(6):790–795. doi: 10.1111/1523-1747.ep12461511. [DOI] [PubMed] [Google Scholar]
- Grøndahl-Hansen J., Ralfkiaer E., Nielsen L. S., Kristensen P., Frentz G., Danø K. Immunohistochemical localization of urokinase- and tissue-type plasminogen activators in psoriatic skin. J Invest Dermatol. 1987 Jan;88(1):28–32. doi: 10.1111/1523-1747.ep12464827. [DOI] [PubMed] [Google Scholar]
- Harvey S. R., Lawrence D. D., Madeja J. M., Abbey S. J., Markus G. Secretion of plasminogen activators by human colorectal and gastric tumor explants. Clin Exp Metastasis. 1988 Nov-Dec;6(6):431–450. doi: 10.1007/BF01784375. [DOI] [PubMed] [Google Scholar]
- Hearing V. J., Law L. W., Corti A., Appella E., Blasi F. Modulation of metastatic potential by cell surface urokinase of murine melanoma cells. Cancer Res. 1988 Mar 1;48(5):1270–1278. [PubMed] [Google Scholar]
- Kaltoft K., Nielsen L. S., Zeuthen J., Danø K. Monoclonal antibody that specifically inhibits a human Mr 52,000 plasminogen-activating enzyme. Proc Natl Acad Sci U S A. 1982 Jun;79(12):3720–3723. doi: 10.1073/pnas.79.12.3720. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kohga S., Harvey S. R., Weaver R. M., Markus G. Localization of plasminogen activators in human colon cancer by immunoperoxidase staining. Cancer Res. 1985 Apr;45(4):1787–1796. [PubMed] [Google Scholar]
- Kristensen P., Hougaard D. M., Nielsen L. S., Danø K. Tissue-type plasminogen activator in rat adrenal medulla. Histochemistry. 1986;85(5):431–436. doi: 10.1007/BF00982674. [DOI] [PubMed] [Google Scholar]
- Kristensen P., Larsson L. I., Nielsen L. S., Grøndahl-Hansen J., Andreasen P. A., Danø K. Human endothelial cells contain one type of plasminogen activator. FEBS Lett. 1984 Mar 12;168(1):33–37. doi: 10.1016/0014-5793(84)80201-x. [DOI] [PubMed] [Google Scholar]
- Kristensen P., Nielsen J. H., Larsson L. I., Danø K. Tissue-type plasminogen activator in somatostatin cells of rat pancreas and hypothalamus. Endocrinology. 1987 Dec;121(6):2238–2244. doi: 10.1210/endo-121-6-2238. [DOI] [PubMed] [Google Scholar]
- Kristensen P., Nielsen L. S., Grøndahl-Hansen J., Andresen P. B., Larsson L. I., Danø K. Immunocytochemical demonstration of tissue-type plasminogen activator in endocrine cells of the rat pituitary gland. J Cell Biol. 1985 Jul;101(1):305–311. doi: 10.1083/jcb.101.1.305. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kristensen P., Pyke C., Lund L. R., Andreasen P. A., Danø K. Plasminogen activator inhibitor-type 1 in Lewis lung carcinoma. Histochemistry. 1990;93(6):559–566. doi: 10.1007/BF00272198. [DOI] [PubMed] [Google Scholar]
- Larsson L. I., Skriver L., Nielsen L. S., Grøndahl-Hansen J., Kristensen P., Danø K. Distribution of urokinase-type plasminogen activator immunoreactivity in the mouse. J Cell Biol. 1984 Mar;98(3):894–903. doi: 10.1083/jcb.98.3.894. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 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]
- Mignatti P., Robbins E., Rifkin D. B. Tumor invasion through the human amniotic membrane: requirement for a proteinase cascade. Cell. 1986 Nov 21;47(4):487–498. doi: 10.1016/0092-8674(86)90613-6. [DOI] [PubMed] [Google Scholar]
- Nielsen L. S., Hansen J. G., Andreasen P. A., Skriver L., Danø K., Zeuthen J. Monoclonal antibody to human 66,000 molecular weight plasminogen activator from melanoma cells. Specific enzyme inhibition and one-step affinity purification. EMBO J. 1983;2(1):115–119. doi: 10.1002/j.1460-2075.1983.tb01391.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Nishino N., Aoki K., Tokura Y., Sakaguchi S., Takada Y., Takada A. The urokinase type of plasminogen activator in cancer of digestive tracts. Thromb Res. 1988 May 15;50(4):527–535. doi: 10.1016/0049-3848(88)90201-0. [DOI] [PubMed] [Google Scholar]
- Ossowski L., Reich E. Antibodies to plasminogen activator inhibit human tumor metastasis. Cell. 1983 Dec;35(3 Pt 2):611–619. doi: 10.1016/0092-8674(83)90093-4. [DOI] [PubMed] [Google Scholar]
- Petersen L. C., Lund L. R., Nielsen L. S., Danø K., Skriver L. One-chain urokinase-type plasminogen activator from human sarcoma cells is a proenzyme with little or no intrinsic activity. J Biol Chem. 1988 Aug 15;263(23):11189–11195. [PubMed] [Google Scholar]
- Reich R., Thompson E. W., Iwamoto Y., Martin G. R., Deason J. R., Fuller G. C., Miskin R. Effects of inhibitors of plasminogen activator, serine proteinases, and collagenase IV on the invasion of basement membranes by metastatic cells. Cancer Res. 1988 Jun 15;48(12):3307–3312. [PubMed] [Google Scholar]
- Roldan A. L., Cubellis M. V., Masucci M. T., Behrendt N., Lund L. R., Danø K., Appella E., Blasi F. Cloning and expression of the receptor for human urokinase plasminogen activator, a central molecule in cell surface, plasmin dependent proteolysis. EMBO J. 1990 Feb;9(2):467–474. doi: 10.1002/j.1460-2075.1990.tb08132.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Sato Y., Rifkin D. B. Inhibition of endothelial cell movement by pericytes and smooth muscle cells: activation of a latent transforming growth factor-beta 1-like molecule by plasmin during co-culture. J Cell Biol. 1989 Jul;109(1):309–315. doi: 10.1083/jcb.109.1.309. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Sim P. S., Stephens R. W., Fayle D. R., Doe W. F. Urokinase-type plasminogen activator in colorectal carcinomas and adenomatous polyps: quantitative expression of active and proenzyme. Int J Cancer. 1988 Oct 15;42(4):483–488. doi: 10.1002/ijc.2910420402. [DOI] [PubMed] [Google Scholar]
- Stephens R. W., Pöllänen J., Tapiovaara H., Leung K. C., Sim P. S., Salonen E. M., Rønne E., Behrendt N., Danø K., Vaheri A. Activation of pro-urokinase and plasminogen on human sarcoma cells: a proteolytic system with surface-bound reactants. J Cell Biol. 1989 May;108(5):1987–1995. doi: 10.1083/jcb.108.5.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 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]
- 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]
- Vassalli J. D., Baccino D., Belin D. A cellular binding site for the Mr 55,000 form of the human plasminogen activator, urokinase. J Cell Biol. 1985 Jan;100(1):86–92. doi: 10.1083/jcb.100.1.86. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Vihko K. K., Kristensen P., Danø K., Parvinen M. Immunohistochemical localization of urokinase-type plasminogen activator in Sertoli cells and tissue-type plasminogen activator in spermatogenic cells in the rat seminiferous epithelium. Dev Biol. 1988 Mar;126(1):150–155. doi: 10.1016/0012-1606(88)90248-5. [DOI] [PubMed] [Google Scholar]
- de Bruin P. A., Griffioen G., Verspaget H. W., Verheijen J. H., Dooijewaard G., van den Ingh H. F., Lamers C. B. Plasminogen activator profiles in neoplastic tissues of the human colon. Cancer Res. 1988 Aug 15;48(16):4520–4524. [PubMed] [Google Scholar]
- de Bruin P. A., Griffioen G., Verspaget H. W., Verheijen J. H., Lamers C. B. Plasminogen activators and tumor development in the human colon: activity levels in normal mucosa, adenomatous polyps, and adenocarcinomas. Cancer Res. 1987 Sep 1;47(17):4654–4657. [PubMed] [Google Scholar]