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(American Journal of Pathology. 2003;163:175-182.)
© 2003 American Society for Investigative Pathology

The Clinical Significance of Cathepsin S Expression in Human Astrocytomas

Thomas Flannery*, David Gibson*, Menakshi Mirakhur{dagger}, Stephen McQuaid{dagger}, Caroline Greenan*, Anne Trimble*, Brian Walker{ddagger}, Derek McCormick* and Patrick G. Johnston*

From the Oncology Department,* Cancer Research Centre, Queen’s University Belfast; the Regional Neuropathology Service,{dagger} Royal Victoria Hospital, Belfast; and the School of Pharmacy,{ddagger} Queen’s University Belfast, Belfast, Ireland, United Kingdom

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.




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