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

Abstract:

: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.

journal_name

Parasitology

journal_title

Parasitology

authors

Adamson RE,Hall FR

doi

10.1017/s0031182000081518

subject

Has Abstract

pub_date

1996-11-01 00:00:00

pages

449-55

eissn

0031-1820

issn

1469-8161

journal_volume

113 ( Pt 5)

pub_type

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