Cathepsin L in glioma progression: Comparison with cathepsin B

Strojnik, Tadej; Kavalar, Rajko; Trinkaus, Miha; Lah, Tamara T.

doi:10.1016/j.cdp.2005.07.006

Cited by 56 publications

(52 citation statements)

References 21 publications

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“…The only previous study of Cat L in brain tumor demonstrated that Cat L expression and activity correlated positively with increased malignancy of human glioma (Sivaparvathi et al, 1996b). We (Strojnik et al, 2005) have confirmed that in gliomas, cathepsin L is found predominantly in the malignant tumor cells. Cat B staining was expressed in both tumor and endothelial cells to the same extent.…”

Section: Cysteine Proteinases Cathepsins B and Lsupporting

confidence: 83%

“…Immunohistochemical staining was performed using the standard technique (Strojnik et al, 1999;Strojnik et al, 2005). The staining for markers was scored separately for the tumor cells, the endothelial cells, and/or the macrophages, as described previously (Strojnik et al, 1999;Strojnik et al, 2005;Strojnik et al, 2007;Strojnik et al, 2009). IHC staining was performed for various marker including cathepsins B and L, nestin, musashi, CD68, kallikrein 6 and Ki-67.…”

Section: Immunohistochemical Staining and Prognostic Impact Of Biologmentioning

confidence: 99%

“…These results suggest that the therapeutic application of cystein proteinase inhibitors should be targeted to both tumor and endothelial cells. To complement our work we measured the expression of cathepsin L in the same population of human glioma patients (Strojnik et al, 2005). Cat L expression is also elevated in various types of human tumors (Lah & Kos, 1998) and its levels were prognostic for survival of patients with breast carcinoma (Thomssen et al, 1995).…”

Section: Cysteine Proteinases Cathepsins B and Lmentioning

confidence: 99%

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Prognostic Significance of Immunohistochemical Markers in Glioma Patients

Strojnik¹

2011

Advances in the Biology, Imaging and Therapies for Glioblastoma

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Section: Cysteine Proteinases Cathepsins B and Lsupporting

confidence: 83%

Section: Immunohistochemical Staining and Prognostic Impact Of Biologmentioning

confidence: 99%

Section: Cysteine Proteinases Cathepsins B and Lmentioning

confidence: 99%

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Prognostic Significance of Immunohistochemical Markers in Glioma Patients

Strojnik¹

2011

Advances in the Biology, Imaging and Therapies for Glioblastoma

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“…We also previously identified lysosomal cathepsins as targets of H2 relaxin, the cognate ligand of RXFP1, and CTRP8 in human thyroid cancer (cathepsin‐D and cathepsin‐L) and GBM (cathepsin‐B), respectively (Glogowska et al ., 2013; Hombach‐Klonisch et al ., 2006). High cathepsin‐B serum levels are associated with poor prognosis in GBM patients (Strojnik et al ., 2005). Stat3 upregulates the expression of lysosomal proteases cathepsin‐B and cathepsin‐L under physiological conditions (Kreuzaler et al ., 2011) and, thus, may facilitate cathepsin‐B enhanced tissue invasion and lysosomal‐mediated cell death regulation in brain tumors (Levicar et al ., 2002).…”

Section: Discussionmentioning

confidence: 99%

C1q/TNF‐related peptide 8 (CTRP8) promotes temozolomide resistance in human glioblastoma

et al. 2018

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The C1q/TNF‐related peptide 8 (CTRP8) has recently emerged as a novel ligand of the G protein‐coupled receptor RXFP1 in the fatal brain tumor glioblastoma (GBM). We previously demonstrated that the CTRP8‐RXFP1 ligand–receptor system promotes motility and matrix invasion of patient GBM and U87 MG cells by specific phosphorylation of PI3 kinase and protein kinase C. Here, we demonstrate a novel role for CTRP8 in protecting human GBM cells against the DNA alkylating damage of temozolomide (TMZ), the standard chemotherapy drug used to treat GBM. This DNA protective role of CTRP8 required a functional RXFP1‐STAT3 signaling cascade in GBM cells. We identified N‐methylpurine DNA glycosylase (MPG), a monofunctional glycosylase that initiates base excision repair pathway by generating an apurinic/apyrimidinic (AP) site, as a new CTRP8‐RXFP1‐STAT3 target in GBM. Upon TMZ exposure, treatment with CTRP8 reduced the formation of AP sites and double‐strand DNA breaks in GBM cells. This CTRP8 effect was independent of cellular MGMT levels and was associated with decreased caspase 3/7 activity and increased survival of human GBM. CTRP8‐induced RXFP1 activation caused an increase in cellular protein levels of the anti‐apoptotic Bcl members and STAT3 targets Bcl‐2 and Bcl‐XL in human GBM. Collectively, our results demonstrate a novel multipronged and clinically relevant mechanism by which the CTRP8‐RXFP1 ligand–receptor system exerts a DNA protective function against TMZ chemotherapeutic stress in GBM. This CTRP8‐RXFP1‐STAT3 axis is a novel determinant of TMZ responsiveness/chemoresistance and an emerging new drug target for improved treatment of human GBM.

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“…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] .…”

Section: Introductionmentioning

confidence: 99%

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

Yang

Wang

et al. 2015

Acta Pharmacol Sin

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Aim: Cathepsin L, a lysosomal cysteine proteinase, is exclusively elevated in a variety of malignancies, including gliomas. In this study we investigated the relationship between cathepsin L and NF-κB, two radiation-responsive elements, in regulating the sensitivity of human glioma cells ionizing radiation (IR) in vitro. Methods: Human glioma U251 cells were exposed to IR (10 Gy), and the expression of cathepsin L and NF-κB was measured using Western blotting. The nuclear translocation of NF-κB p65 and p50 was analyzed with immunofluorescence assays. Cell apoptosis was examined with clonogenic assays. NF-κB transcription and NF-κB-dependent cyclin D1 and ATM transactivation were monitored using luciferase reporter and ChIP assays, respectively. DNA damage repair was investigated using the comet assay.

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Cathepsin L in glioma progression: Comparison with cathepsin B

Cited by 56 publications

References 21 publications

Prognostic Significance of Immunohistochemical Markers in Glioma Patients

Prognostic Significance of Immunohistochemical Markers in Glioma Patients

C1q/TNF‐related peptide 8 (CTRP8) promotes temozolomide resistance in human glioblastoma

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

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