The clinical significance of cathepsin S expression in human astrocytomas

Thomas Flannery, David Gibson, Menakshi Mirakur, Stephen McQuaid, Caroline Greenan, Trimble Anne, Brian Walker, Derek McCormick, Patrick G. Johnston

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Abstract

Early local invasion by astrocytoma cells results in tumor recurrence even after apparent total surgical resection, leading to the poor prognosis associated with malignant astrocytomas. Proteolytic enzymes have been implicated in facilitating tumor cell invasion and the current study was designed to characterize the expression of the cysteine proteinase cathepsin S (CatS) in astrocytomas and examine its potential role in invasion. Immunohistochemical analysis of biopsies demonstrated that CatS was expressed in astrocytoma cells but absent from normal astrocytes, oligodendrocytes, neurones and endothelial cells. Microglial cells and macrophages were also positive. Assays of specific activity in 59 astrocytoma biopsies confirmed CatS expression and in addition demonstrated that the highest levels of activity were expressed in grade IV tumors. CatS activity was also present in astrocytoma cells in vitro and the extracellular levels of activity were highest in cultures derived from grade IV tumors. In vitro invasion assays were carried out using the U251MG cell line and the invasion rate was reduced by up to 61% in the presence of the selective CatS inhibitor 4-Morpholineurea-Leu-HomoPhe-vinylsulphone. We conclude that CatS expression is up-regulated in astrocytoma cells and provide evidence for a potential role for CatS in invasion.
Original languageEnglish
Pages (from-to)175-182
JournalAmerican Journal of Pathlogy
Volume163
Issue number1
DOIs
Publication statusPublished - 2003

Keywords

  • Astrocytoma
  • Cysteine proteinases
  • tumour invasion

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