Abstract:Alterations in dipeptidyl peptidase-IV (DPP-IV) enzymatic activity are characteristic of malignant transformation. Through its well-characterized functionality in regulating the activity of bioactive peptides by removal of the N-terminal dipeptide, DPP-IV activity may have profound effects upon metastatic potential and cell growth. Although DPP-IV/CD26 (EC 3.4.14.5) is the canonical representative of the group, a number of other proteins including DPP-7, 8, 9, and seprase/fibroblast activation protein-α (FAP-α… Show more
“…1); for DPP-IV, the quantity determined by ELISA correlated with the DPP-IV enzymatic activity in tissue homogenates (r=0.79, P<0.05, data not shown). These data confirmed our previously reported results 11 in an independent patient cohort.…”
Section: Expression Of Dpp-iv and Fap Increases With Increasing Gliomsupporting
confidence: 83%
“…FAP immunopositivity was detectable by WB in most of the high-grade glioma samples, but was absent in the DPP-IV negative gliomas. This is consistent with ours as well as other authors' reports suggesting the coexpression and possible coregulation of DPP-IV and FAP in glioma cells and tissues 11,31 , human pancreatic alpha cells 37 and in some cancer cell lines 38 . The coexpression of DPP-IV and FAP was also described in endothelial cells, where both molecules are part of proteolytically active heteromeric aggregates with a molecular weight of 820 kDa, promoting cell migration and invasion 30 .…”
supporting
confidence: 82%
“…Both proteases are involved in the regulation of cell differentiation, adhesion and migration by their proteolytic activity and also non-hydrolytic interactions 9,10 . Our previous reports demonstrated that the expression DPP-IV and FAP is increased in glioblastomas 11,12 . The data on their pathogenetic role in brain tumors is limited-DPP-IV inhibits glioma cell growth, in large part independently of its enzymatic activity 13 , and FAP likely influences the interaction of glioma cells with the surrounding extracellular matrix (our unpublished results and ref.…”
Background and Aims. Proteolytic enzymes contribute to the progression of various cancers. We previously reported increased expression of the proline specific peptidases dipeptidyl peptidase-IV (DPP-IV) and its closest paralogue fibroblast activation protein (FAP) in human glioblastomas. Here we analyze the molecular heterogeneity of DPP-IV and FAP in glioblastomas. Methods. ELISA, isoelectric focusing, 1D and 2D electrophoresis followed by WB or enzyme overlay assay were utilized to analyze DPP-IV and FAP isoforms. Cell fractionation using a Percoll gradient and deglycosylation with PNGase F were performed to analyze the possible basis of DPP-IV and FAP microheterogeneity. Results. Molecular forms of DPP-IV with an estimated molecular weight of 140-160 kDa and a pI predominantly 5.8 were detected in human glioblastoma; in some tumors additional isoforms with a more acidic (3.5-5.5) as well as alkaline (8.1) pI were revealed. Using 2D electrophoresis, two to three molecular forms of FAP with an alkaline (7.0-8.5) pI and an estimated MW of 120-140 kDa were identified in glioblastoma tissues. In glioma cell lines in vitro, several isoforms of both enzymes were expressed, however the alkalic forms present in glioblastoma tissues were not detected. Removal of N-linked oligosaccharides decreased the estimated molecular weight of both enzymes; the overall pattern of molecular forms nevertheless remained unchanged. Conclusion. Several isoforms of DPP-IV and FAP are present in glioblastoma tissue. The absence of alkaline isoforms of both enzymes in glioma cell lines however suggests that isoforms from other, most likely stromal, cell types contribute to the overall pattern seen in glioblastoma tissues.
“…1); for DPP-IV, the quantity determined by ELISA correlated with the DPP-IV enzymatic activity in tissue homogenates (r=0.79, P<0.05, data not shown). These data confirmed our previously reported results 11 in an independent patient cohort.…”
Section: Expression Of Dpp-iv and Fap Increases With Increasing Gliomsupporting
confidence: 83%
“…FAP immunopositivity was detectable by WB in most of the high-grade glioma samples, but was absent in the DPP-IV negative gliomas. This is consistent with ours as well as other authors' reports suggesting the coexpression and possible coregulation of DPP-IV and FAP in glioma cells and tissues 11,31 , human pancreatic alpha cells 37 and in some cancer cell lines 38 . The coexpression of DPP-IV and FAP was also described in endothelial cells, where both molecules are part of proteolytically active heteromeric aggregates with a molecular weight of 820 kDa, promoting cell migration and invasion 30 .…”
supporting
confidence: 82%
“…Both proteases are involved in the regulation of cell differentiation, adhesion and migration by their proteolytic activity and also non-hydrolytic interactions 9,10 . Our previous reports demonstrated that the expression DPP-IV and FAP is increased in glioblastomas 11,12 . The data on their pathogenetic role in brain tumors is limited-DPP-IV inhibits glioma cell growth, in large part independently of its enzymatic activity 13 , and FAP likely influences the interaction of glioma cells with the surrounding extracellular matrix (our unpublished results and ref.…”
Background and Aims. Proteolytic enzymes contribute to the progression of various cancers. We previously reported increased expression of the proline specific peptidases dipeptidyl peptidase-IV (DPP-IV) and its closest paralogue fibroblast activation protein (FAP) in human glioblastomas. Here we analyze the molecular heterogeneity of DPP-IV and FAP in glioblastomas. Methods. ELISA, isoelectric focusing, 1D and 2D electrophoresis followed by WB or enzyme overlay assay were utilized to analyze DPP-IV and FAP isoforms. Cell fractionation using a Percoll gradient and deglycosylation with PNGase F were performed to analyze the possible basis of DPP-IV and FAP microheterogeneity. Results. Molecular forms of DPP-IV with an estimated molecular weight of 140-160 kDa and a pI predominantly 5.8 were detected in human glioblastoma; in some tumors additional isoforms with a more acidic (3.5-5.5) as well as alkaline (8.1) pI were revealed. Using 2D electrophoresis, two to three molecular forms of FAP with an alkaline (7.0-8.5) pI and an estimated MW of 120-140 kDa were identified in glioblastoma tissues. In glioma cell lines in vitro, several isoforms of both enzymes were expressed, however the alkalic forms present in glioblastoma tissues were not detected. Removal of N-linked oligosaccharides decreased the estimated molecular weight of both enzymes; the overall pattern of molecular forms nevertheless remained unchanged. Conclusion. Several isoforms of DPP-IV and FAP are present in glioblastoma tissue. The absence of alkaline isoforms of both enzymes in glioma cell lines however suggests that isoforms from other, most likely stromal, cell types contribute to the overall pattern seen in glioblastoma tissues.
“…In clinical samples high levels of FAP expression have been associated with poor outcome in colorectal and ovarian cancer but improved outcome in invasive ductal breast carcinoma [1,10,50]. While expression of FAP in human astrocytic tumors has been reported, with increased expression correlating with increased grade [33], further investigation of this gene and its association with chemosensitivity is needed to reveal its role in gliomagenesis.…”
Abstract.Background: Oligodendroglial tumors with 1p/19q loss are more likely to be chemosensitive and have longer survival than those with intact 1p/19q, but not all respond to chemotherapy, warranting investigation of the biological basis of chemosensitivity.Methods: Gene expression profiling was performed using amplified antisense RNA from 28 oligodendroglial tumors treated with chemotherapy (26 serial stereotactic biopsy, 2 resection). Expression of differentially expressed genes was validated by real-time PCR.Results: Unsupervised hierarchical clustering showed clustering of multiple samples from the same case in 14/17 cases and identified subgroups associated with tumor grade and 1p/19q status. 176 genes were differentially expressed, 164 being associated with 1p/19q loss (86% not on 1p or 19q). 94 genes differed between responders and non-responders to chemotherapy; 12 were not associated with 1p/19q loss. Significant differential expression was confirmed in 11/13 selected genes. Novel genes associated with response to therapy included SSBP2, GFRA1, FAP and RASD1. IQGAP1, INA, TGIF1, NR2F2 and MYCBP were differentially expressed in oligodendroglial tumors with 1p/19q loss.Conclusion: Gene expression profiling using serial stereotactic biopsies indicated greater homogeneity within tumors than between tumors. Genes associated with 1p/19q status or response were identified warranting further elucidation of their role in oligodendroglial tumors.
“…In selected carcinoma tissues, CD26 is misexpressed and it can function either as an oncogene or as a tumour suppressor gene. Its expression is upregulated and associated with tumour aggressiveness in T and B lymphomas and leukaemias (Bauvois et al, 1999;Carbone et al, 1995;Dang et al, 2003), thyroid follicular tumours (de Micco et al, 2008), papillary carcinomas, astrocytic tumours (Stremenova et al, 2007) and gastrointestinal stromal tumours (Yamaguchi et al, 2008). Conversely, loss of CD26 occurs during malignant transformation of melanocytes into melanoma (Wesley et al, 1999), indicating a possible role of the molecule in suppressing the malignant transformation of melanocytes.…”
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