The role of the cysteine proteinase cathepsin S in astrocytoma invasion

Introduction: Local tumour invasion gives rise to recurrence after surgical resection, leading to the poor prognosis associated with malignant astrocytomas. Extracellular proteolytic enzymes including cysteine proteinases have been implicated in facilitating tumour cell invasion. The current study was designed to characterize the expression of the cysteine proteinase, cathepsin S and investigate its potential role in the invasive process.Materials and methods: Expression of cathepsin S was investigated in astrocytoma biopsies by immunohistochemistry and in astrocytoma cultures by immunocytochemistry and the reverse transcription polymerase chain reaction. Cathepsin S activity assays were also performed on in vitro and in vivo samples. An in vitro Matrigel invasion assay was used to evaluate the effect of selective cathepsin S inactivation, by the inhibitor LHVS, on glioblastoma cell invasion.Results: Cathepsin S immunostaining was restricted to tumour cells in vivo. Cathepsin S transcript, protein and activity were observed within astrocytoma cells in vitro. Extracellular cathepsin S activity was about five-fold higher in cultures from grade IV tumours than in lower grades. Inhibition of cathepsin S with 0.01 µm LHVS significantly inhibited in vitro invasion of the glioblastoma cell line U251 mg by 50% (P <0.0001).Conclusions: It has been demonstrated for the first time that cathepsin S is expressed and secreted by astrocytoma cells and plays a role in astrocytoma invasion, and is therefore a potential therapeutic target.