Clinical and Experimental Studies of Cysteine Cathepsins and Their Inhibitors in Human Brain Tumors

Selective suppression of cathepsin L by antisense cDNA impairs human brain tumor cell invasion in vitro and promotes apoptosis

“…In a previous study, we demonstrated that penetration of glioblastoma cells into these protein substrates in an in vitro invasion assay was significantly impaired by a general cysteine proteases inhibitor E -64c and by intracellular and extracellular inhibition of cathepsin B by its selective inhibitors, Ca074Me and Ca074, respectively. 10 However, the impairment of inhibition was not complete, suggesting that other endopeptidases, including another cysteine peptidases, were involved. Indeed, CLIK 148, a specific cathepsin L inhibitor, also reduced the invasion of tumor cells through Matrigel.…”

“…We have previously demonstrated that cathepsin L protein levels and activity were significantly higher in anaplastic astrocytoma and glioblastoma cell lines than in benign astrocytomas, although the relative role of cathepsin L in local invasion is not known. 10 One of the most important aspects of therapeutic failure in malignant brain tumors is the high resistance of glioma cells to induction of apoptosis, which should be triggered by chemotherapy and/ or radiation therapy. Malfunctions of apoptotic signaling pathways are common in many forms of human cancers, 11 as cancer cells have raised apoptotic thresholds.…”

Prognostic Significance of Immunohistochemical Markers in Glioma Patients

“…Differently from other reports, we performed immunohistochemical staining for the panel of markers on the same group of patients. Increased expression of lysosomal cystein proteinases such as cathepsins B and L plays a functional role in tumor cell migration and metastasis (Lah et al, 2000). We found that Cat B expression was highly elevated in GBM compared to lower grade malignant tumors and benign tumors.…”

“…It was proposed that nestin plays a role in tumor invasion of melanomas (Florenes et al, 1994, as cited in Strojnik et al, 2007). Nestin may therefore correlate with other markers of invasiveness, such as cysteine cathepsins B and L, which are both highly up-regulated in high-grade gliomas (Lah et al, 2000;Levičar et al, 2002;Sivaparvathi et al, 1995). In our study, a positive correlation between Cat B and nestin was established in high-grade gliomas, both markers correlating with the malignancy, as defined by histological scores.…”

Inhibition of cathepsin L sensitizes human glioma cells to ionizing radiation in vitro through NF-κB signaling pathway

“…Cathepsin L is a survival protein that confers resistance to cancer cell apoptosis [22,23] . The expression of cathepsin L is exclusively elevated in cancer cells and can be easily screened for small-molecule inhibitors [24,25] ; therefore, it may serve as a better therapeutic target than other cathepsins [26][27][28] .…”