Skip to main content Accessibility help
×
Home
Hostname: page-component-5bf98f6d76-nn2qz Total loading time: 0.447 Render date: 2021-04-21T18:36:52.126Z Has data issue: true Feature Flags: { "shouldUseShareProductTool": true, "shouldUseHypothesis": true, "isUnsiloEnabled": true, "metricsAbstractViews": false, "figures": false, "newCiteModal": false, "newCitedByModal": true }

Article contents

Matrix metalloproteinases mediate the metastatic phenotype of Theileria annulata-transformed cells

Published online by Cambridge University Press:  06 April 2009

R. E. Adamson
Affiliation:
Department of Biology, PO Box 373, University of York, York YO1 5YW, UK
F. R. Hall
Affiliation:
Department of Biology, PO Box 373, University of York, York YO1 5YW, UK

Summary

Theileria annulata infects and reversibly transforms bovine leucocytes. The parasite-transformed cells are immortalized, metastatic and express a number of metalloproteinases including matrix metalloproteinase 9 which they secrete. All the metalloproteinases observed on substrate gels are inhibited by tissue inhibitor of metalloproteinase 1 and 4 synthetic inhibitors BB94, GM6001, BRL29808AI and Ro31–4724. We have adapted an in vitro assay for metastatic behaviour that measures the ability of parasitized cells to cross reconstituted basement membrane, Matrigel™. Using this we demonstrated that macroschizont-infected cells are invasive in vitro and that their invasive properties can be almost eliminated by the same specific inhibitors of metalloproteinases as used in the substrate gels. This demonstrates that the metastatic behaviour of the infected cells is due in part to metalloproteinase activity and strongly suggests a role for the metalloproteinases we observed on gels. This is further supported by the fact that an attenuated vaccine line which shows much reduced metalloproteinase activity also exhibits a marked reduction in metastatic behaviour. We suggest that these metalloproteinases are virulence factors mediating some pathological features of the disease and their loss in the vaccine line could provide an explanation for attenuation.

Type
Research Article
Copyright
Copyright © Cambridge University Press 1996

Access options

Get access to the full version of this content by using one of the access options below.

References

Agren, M. S., Taplin, C. J., Woessner, J. F., Eaglestein, W. H. & Mertz, P. M. (1992). Collagenasc activity during wound-healing. Journal of Investigative Dermatology 98, 612621.Google Scholar
Alvarez, O. A., Carmichael, D. F. & Declerk, Y. A. (1990). Inhibition of collagenolytic activity and metastasis of tumour cells by a recombinant human tissue inhibitor of metalloproteinases. Journal of the National Cancer Institute 82, 589595.CrossRefGoogle ScholarPubMed
Anderson, C. W., Baum, P. R. & Gesteland, R. F. (1973). Processing of adenovirus-2 induced proteins. Journal of Virology 12, 241252.Google ScholarPubMed
Baylis, H. A., Megson, A., Brown, C. G. D., Wilkie, G. F. & Hall, F. R. (1992). Theileria annulata-infected cells produce abundant proteases whose activity is reduced by long-term culture. Parasitology 105, 417423.CrossRefGoogle Scholar
Baylis, H. A., Megson, A. & Hall, F. R. (1995). Infection with Theileria annulata induces expression of matrix metalloproteinase 9 and transcription factor AP-1 in bovine leucocytes. Molecular and Biochemical Parasitology 69, 211222.CrossRefGoogle ScholarPubMed
Birkedal-Hansen, H. (1995). Proteolytic remodelling of extracellular matrix. Current Opinions in Cell Biology 7, 728735.CrossRefGoogle Scholar
Bradford, M. M. (1976). A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Analytical Biochemistry 72, 284–254.CrossRefGoogle ScholarPubMed
Brown, C. G. D. (1987). Theileriidae. In In vitro Methods for Parasite Cultivation (ed. Taylor, A. E. R. & Baker, J. R.), pp. 230253. Academic Press, London.Google Scholar
Brown, P. D. (1995). Matrix metalloproteinase inhibitors: a novel class of anticancer agents. Advances in Enzyme Regulation 35, 293301.CrossRefGoogle ScholarPubMed
Brown, W. C., Shaw, M. K., Conrad, P. A. & Dolan, T. T. (1989). Theileria parva: Reappearance of schizonts in infected lymphoblastoid cells treated with parvaquone is dependent on interleukin 2-like growth factors. Experimental Parasitology 68, 308325.CrossRefGoogle ScholarPubMed
Cawston, T. E., Murphy, G. M., Mercer, E., Galloway, W. A., Hazelman, B. L. & Reynolds, J. J. (1983). The interaction of purified rabbit bone collagenase with purified rabbit bone metalloproteinase inhibitor. The Biochemical Journal 211, 313318.CrossRefGoogle ScholarPubMed
Cawston, T. E. (1995). Proteinases and inhibitors. British Medical Bulletin 51, 385401.CrossRefGoogle ScholarPubMed
Davies, B., Brown, P. D., East, N., Crimmin, M. J. & Balkwill, F. R. (1993). A synthetic matrix metalloproteinase inhibitor decreases tumour burden and prolongs survival of mice bearing ovarian carcinoma xenografts. Cancer Research 53, 20872091.Google ScholarPubMed
Denhardt, D. T., Feng, B., Edwards, D. R., Cocuzzi, E. T. & Malyankar, U. M. (1993). Tissue inhibitor of metalloproteinase (TIMP, aka EPA): structure, control of expression and biological functions. Pharmacology and Therapeutics 59, 329341.CrossRefGoogle ScholarPubMed
Dschunkowsky, E. & Luhs, J. (1904) Die Piroplasmosen der Rinder. Zentralblatt für Bakteriologie, Parasitenkunde, Infektionskrankheit und Hygiene, Abt I 35, 486493.Google Scholar
Fell, A. H., Preston, P. M. & Ansell, J. D. (1990). Establishment of Theileria-infected bovine cell lines in SCID mice. Parasite Immunology 12, 335339.CrossRefGoogle ScholarPubMed
Gearing, A. J. H., Beckett, P., Christodoulou, M., Churchill, M., Clements, J., Davidson, A. H., Drummond, A. H., Galloway, W. A., Gilbert, R. & Gordon, J. J. (1994). Processing of tumour necrosis factor-alpha precursor by metalloproteinases. Nature, London 370, 555557.CrossRefGoogle ScholarPubMed
Gearing, A. J. H., Beckett, P., Christodoulou, M., Churchill, M., Clements, J. M., Crimmin, M., Davidson, A. H., Drummond, A. H., Galloway, W. A., Gilbert, R., Gordon, J. J., Leber, T. M., Mangan, M., Miler, K., Nayee, P., Owen, K., Patel, S., Thomas, W., Wells, G., Wood, L. M. & Woolley, K. (1995). Matrix metalloproteinases and processing of pro-TNF-α. Journal of Leukocyte Biology 57, 774777.Google ScholarPubMed
Hendrix, M. J., Wood, W. R., Seftor, E. A., Lotan, D., Nakajima, M., Misiorowski, R. L., Seftor, R. E., Stetler-Stevenson, W. G., Bevaqua, S. J. & Liotta, L. A. (1990). Retinoic acid inhibition of human melanoma cell invasion through a reconstituted basement membrane and its relation to decreases in the expression of proteolytic enzymes and motility factor receptor. Cancer Research 50, 41214130.Google ScholarPubMed
Herlyn, D., Iliopoulos, D., Jensen, P. J., Parmiter, A., Baird, J., Hotta, H., Adachi, K., Ross, A. H., Jambrosic, J., Koprowski, H. & Herlyn, M. (1990). In vitro properties of human melanoma cells metastatic in nude mice. Cancer Research 50, 22962302.Google ScholarPubMed
Irvin, A. D. & Morrison, W. I. (1987). Immunopathology, immunology and immunoprophylaxis of Theileria infections. In Immune Responses in Parasitic Infections: Immunology, Immunopathology and Immunoprophylaxis, vol. III. Protozoa, (ed. Souslby, E. J. L.) pp. 223274. CRC Press Inc., Baton Rouge, Florida.Google Scholar
Kohn, E. C. & Liotta, L. A. (1995). Molecular insights into cancer invasion: strategies for prevention and intervention. Cancer Research 55, 18561862.Google ScholarPubMed
Laemmli, U. K. (1970). Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature, London 227, 680685.CrossRefGoogle ScholarPubMed
Leppert, D., Waubant, E., Galardy, R., Bunnett, N. W. & Hauser, S. L. (1995). T cell gelatinases mediate basement membrane transmigration in vitro. Journal of Immunology 154, 43794389.Google ScholarPubMed
McGeehan, G. M., Becherer, J. D., Bast, R. C., Boyer, C. M. Jr, Champion, B., Connolly, K. M., Conway, J. G., Furdon, P., Karp, S. & Kidao, S. (1994). Regulation of tumour necrosis factor-alpha processing by a metalloproteinase inhibitor. Nature, London 370, 558561.CrossRefGoogle ScholarPubMed
Moore, W. M. & Spilburg, C. A. (1986). Peptide hydroxamic acids inhibit skin collagenases. Biochemical and Biophysical Research Communications 136, 390395.CrossRefGoogle Scholar
Nakajima, M., Lotan, D., Baig, M. M., Carralero, R. M., Wood, W. R., Hendrix, M. J. C. & Lotan, R. (1989). Inhibition by retinoic acid of type IV collagenolysis and invasion through reconstituted basement membrane by metastatic rat mammary adenocarcinoma cells. Cancer Research 49, 16981706.Google ScholarPubMed
Okada, Y., Nagase, H. & Harris, E. D. Jr (1987). Matrix metalloproteinase 1, 2, and 3 from rheumatoid synovial cells are sufficient to destroy joints. Journal of Rheumatology 14, 4142.Google Scholar
Preston, P. M., Brown, C. G. D., Entrican, G., Richardson, W. & Boid, R. (1993). Synthesis of tumour necrosis factor-alpha and interferons by mononuclear cells from Theileria annulata-infected cattle. Parasite Immunology 15, 525534.CrossRefGoogle ScholarPubMed
Reponen, P., Sahlberg, C., Huatala, P., Hurskainen, T., Thesleff, I. & Tryggvaso, K. (1992). Molecular cloning of murine 72-kDa type IV collagenase and its expression during mouse development. Journal of Biological Chemistry 267, 78567862.Google ScholarPubMed
Schultz, G. S., Strelow, S., Stern, G. A., Chegini, N., Grant, M. B., Galardy, R. E., Grobelny, D., Rowsey, J. J., Stonecipher, K., Parmley, V. & Khaw, P. T. (1992). Treatment of alkali-injured rabbit corneas with a synthetic inhibitor of matrix metalloproteinases. Investigative Ophthalmology and Visual Science 33, 33253331.Google ScholarPubMed
Stetler-Stevenson, W. G., Aznavoorian, S. & Liotta, L. A. (1993). Tumour cell interactions with the extracellular matrix during invasion and metastasis. Annual Revue of Cell Biology 9, 541573.CrossRefGoogle ScholarPubMed
Terranova, V. P., Hujanen, E. S., Loeb, D. M., Martin, G. R., Thornburg, L. & Glushko, V. (1986). Use of a reconstituted basement membrane to measure cell invasiveness and select for highly invasive tumour cells. Proceedings of the National Academy of Sciences, USA 83, 465469.CrossRefGoogle Scholar

Full text views

Full text views reflects PDF downloads, PDFs sent to Google Drive, Dropbox and Kindle and HTML full text views.

Total number of HTML views: 0
Total number of PDF views: 10 *
View data table for this chart

* Views captured on Cambridge Core between September 2016 - 21st April 2021. This data will be updated every 24 hours.

Send article to Kindle

To send this article to your Kindle, first ensure no-reply@cambridge.org is added to your Approved Personal Document E-mail List under your Personal Document Settings on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part of your Kindle email address below. Find out more about sending to your Kindle. Find out more about sending to your Kindle.

Note you can select to send to either the @free.kindle.com or @kindle.com variations. ‘@free.kindle.com’ emails are free but can only be sent to your device when it is connected to wi-fi. ‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.

Find out more about the Kindle Personal Document Service.

Matrix metalloproteinases mediate the metastatic phenotype of Theileria annulata-transformed cells
Available formats
×

Send article to Dropbox

To send this article to your Dropbox account, please select one or more formats and confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your <service> account. Find out more about sending content to Dropbox.

Matrix metalloproteinases mediate the metastatic phenotype of Theileria annulata-transformed cells
Available formats
×

Send article to Google Drive

To send this article to your Google Drive account, please select one or more formats and confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your <service> account. Find out more about sending content to Google Drive.

Matrix metalloproteinases mediate the metastatic phenotype of Theileria annulata-transformed cells
Available formats
×
×

Reply to: Submit a response


Your details


Conflicting interests

Do you have any conflicting interests? *