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

Hyaluronan binding to its cellular receptors CD44 and ICAM-1 appears to enhance the malignant behavior of tumors, including astrocytomas. RHAMM/IHABP, another hyaluronan receptor, has been identified in breast carcinoma cells, but its presence in astrocytomas is yet undetermined. Herein, we report that a monoclonal antibody against plectin (a cytoskeletal protein linker) recognizes on Western blots of U-373 MG glioblastoma cells, a 300-kDa band corresponding to plectin and two bands of 86 and 70 kDa. cDNA cloning and Northern blotting reveals that these two bands represent isoforms of RHAMM/IHABP. Sequence comparisons suggest that the plectin monoclonal antibody recognizes RHAMM/IHABP because this protein and plectin share short peptide sequences of similar primary and secondary structure. Western blotting demonstrates that most human astrocytoma tissues and cell lines express the 86- and 70-kDa isoforms of RHAMM/IHABP. Interestingly, the 70-kDa variant is undetectable in normal brain tissues and in primary cultures of astrocytes suggesting that its expression is tumor-specific. Transfection experiments with epitope-tagged RHAMM/IHABP cDNA established that RHAMM/IHABP associates with microtubules in astrocytoma cells, while in normal astrocytes it either co-localizes with microtubules or has a diffuse cytoplasmic distribution. This suggests that RHAMM/IHABP has the capacity to bind to microtubules in normal and transformed astrocytes, and that neoplasia may favor this association.
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PMID:The hyaluronan receptor RHAMM/IHABP in astrocytoma cells: expression of a tumor-specific variant and association with microtubules. 1222 34

Glioblastoma (GBM) is both the most common and the most lethal primary brain tumor. It is thought that GBM stem cells (GSCs) are critically important in resistance to therapy. Therefore, there is a strong rationale to target these cells in order to develop new molecular therapies.To identify molecular targets in GSCs, we compared gene expression in GSCs to that in neural stem cells (NSCs) from the adult human brain, using microarrays. Bioinformatic filtering identified 20 genes (PBK/TOPK, CENPA, KIF15, DEPDC1, CDC6, DLG7/DLGAP5/HURP, KIF18A, EZH2, HMMR/RHAMM/CD168, NOL4, MPP6, MDM1, RAPGEF4, RHBDD1, FNDC3B, FILIP1L, MCC, ATXN7L4/ATXN7L1, P2RY5/LPAR6 and FAM118A) that were consistently expressed in GSC cultures and consistently not expressed in NSC cultures. The expression of these genes was confirmed in clinical samples (TCGA and REMBRANDT). The first nine genes were highly co-expressed in all GBM subtypes and were part of the same protein-protein interaction network. Furthermore, their combined up-regulation correlated negatively with patient survival in the mesenchymal GBM subtype. Using targeted proteomics and the COGNOSCENTE database we linked these genes to GBM signalling pathways.Nine genes: PBK, CENPA, KIF15, DEPDC1, CDC6, DLG7, KIF18A, EZH2 and HMMR should be further explored as targets for treatment of GBM.
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PMID:Combined expressional analysis, bioinformatics and targeted proteomics identify new potential therapeutic targets in glioblastoma stem cells. 2629 6