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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
*
*Corresponding author. Tel: 01904 432864. Fax: 01904 432860.

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

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