Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0017636 (glioblastoma)
 18,345 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Malignant glioma is characterized by rapid proliferation, high invasiveness into the surrounding brain and increased vascularity. The aim of the study was to explain the observation that glioblastoma invasion often occurs along existing vasculature, suggesting interactions between the two types of cells. Using the in vitro model, we demonstrate that co-culturing of U87 (human glioblastoma) cells with HMEC-1 (human microvascular endothelial) cells increases the invasiveness of the U87 cells. The enhanced invasiveness correlates with increased expression of MMP-9 in both U87 and HMEC-1 cells, increased expression of cysteine cathepsins B and S and down-regulation of endogenous cell adhesion molecule NCAM in U87 cells. On the other hand, U87 tumour cells significantly enhance the proliferation of co-cultured endothelial cells by a mechanism involving cathepsin B, but not cathepsin S. Furthermore, we demonstrated that increased cell expression and activity of MMP-9 in cell microenvironment is mediated via secretion of SDF-1 by HMEC-1 cells. Selective SDF-1 inhibition impaired the enhanced U87 cell invasion, mostly via down-regulation of MMP-9, but did not alter cathepsin B, although the latter is more relevant for the invasion of U87 cells in mono-culture. Taken together, our study suggests that glioblastoma cells may be attracted by endothelial cells, enhancing their proliferation and underlines the importance of SDF-1, cathepsin B and MMP-9 in the cross-talk between these cells in normoxic conditions. This notion contributes to better understanding and suggests further investigations of the paracrine mechanisms, regulating glioma angiogenesis.
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PMID:Glioblastoma and endothelial cells cross-talk, mediated by SDF-1, enhances tumour invasion and endothelial proliferation by increasing expression of cathepsins B, S, and MMP-9. 1970 Feb 39

Cathepsin S is a lysosomal cysteine protease that is overexpressed in various cancer models and plays important role in tumorigenesis, however the mechanisms are unclear. In the present study, we found that inhibition of cathepsin S induced autophagy and mitochondrial apoptosis in human glioblastoma cells. Blockade of autophagy by either a chemical inhibitor or RNA interference attenuated cathespin S inhibition-induced apoptosis. Furthermore, autophagy and apoptosis induction was dependent on the suppression of phosphatidylinositide 3-kinases/protein kinase B/mammalian target of rapamycin/p70S6 kinase (PI3K/AKT/mTOR/p70S6K) signaling pathway and activation of c-Jun N-terminal kinase (JNK) signaling pathway. In addition, reactive oxygen species (ROS) served as an upstream of PI3K/AKT/mTOR/p70S6K and JNK signaling pathways. In conclusion, the current study revealed that cathepsin S played an important role in the regulation of autophagy and apoptosis in human glioblastoma cells.
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PMID:Inhibition of cathepsin S induces autophagy and apoptosis in human glioblastoma cell lines through ROS-mediated PI3K/AKT/mTOR/p70S6K and JNK signaling pathways. 2487 36

Objective To investigate the expression of cathepsin S (CTSS) in temozolomide-resistant glioblastoma T98G (T98G-R) cells. Methods The differentially expressed genes involved in T98G-R cells were obtained from NCBI database, and the expression of CTSS in glioblastoma was analyzed in Gene Expression Profiling Interactive Analysis (GEPIA2) and Chinese Glioma Genome Atlas (CGGA) database. Real-time quantitative PCR and Western blot analysis were used to detect CTSS expression in T98G cells and T98G-R cells. The correlation between CTSS expression level and patient prognosis was analyzed using the Cancer Genome Atlas (TCGA) database. Results Gene CTSS was screened out by comparing the differentially expressed genes in T98G-R cells using NCBI GEO chip data GSE2221. GEPIA2 database analysis showed higher CTSS expression in glioblastoma tissues than in normal tissues. Both mRNA and protein levels of CTSS in T98G-R cells were significantly higher than those in T98G cells. TCGA database showed that GBM patients with high CTSS expression exhibited poorer prognosis. Conclusion CTSS is highly expressed in T98G-R cells and is associated with poor prognosis in patients.
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PMID:[Cathepsin S (CTSS) is highly expressed in temozolomide-resistant glioblastoma T98G cells and associated with poor prognosis]. 3314 88