Coupled expression of dipeptidyl peptidase-IV and fibroblast activation protein-α in transformed astrocytic cells

Balážiová, Eva; Bušek, Petr; Stremeňová, Jarmila; Sromova, Lucie; Kr̆epela, E; Lizcova, Libuse; Šedo, Aleksi

doi:10.1007/s11010-011-0828-z

Cited by 18 publications

(17 citation statements)

References 20 publications

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“…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 .…”

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confidence: 94%

“…D) Effect of deglycosylation on the electrophoretic mobility of DPP-IV and FAP molecular forms expressed in human glioma cell lines. PNGase F= peptide N-glycosidase F fraction, possibly in the form of high molecular weight oligomeric complexes 30,31 . However, in addition to the plasma membrane, both DPP-IV and FAP are also localized in various intracellular compartments 32,33 (Fig.…”

Section: Possible Basis Of the Heterogeneity Of Dpp-iv And Fap Molecumentioning

confidence: 99%

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Heterogeneity of molecular forms of dipeptidyl peptidase-IV and fibroblast activation protein in human glioblastomas

et al. 2017

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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.

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confidence: 94%

Section: Possible Basis Of the Heterogeneity Of Dpp-iv And Fap Molecumentioning

confidence: 99%

Heterogeneity of molecular forms of dipeptidyl peptidase-IV and fibroblast activation protein in human glioblastomas

et al. 2017

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“…Interestingly, we identified a moderate negative, non-reciprocal correlation between the level of expressed FAP protein and DP4 mRNA in breast and ovarian cancer cell lines but found no correlation between FAP and DP4 mRNA. Both DP4 and FAP are located adjacent to each other on the long arm of chromosome 2 (52) and their co-transcriptional regulation has been previously suggested (53). The identification of a negative correlation between FAP protein and DP4 mRNA and protein may suggest that, similar to DP9, DP4-dependent post-transcriptional regulation of FAP is occurring in breast and ovarian cancer cell lines.…”

Section: Discussionmentioning

confidence: 88%

Expression profiling of dipeptidyl peptidase 8 and 9 in breast and ovarian carcinoma cell lines

Wilson

Abbott

2012

International Journal of Oncology

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Abstract. Proteases, particularly serine proteases like dipeptidyl peptidase 4 (DP4) and fibroblast activation protein (FAP), play an important role in cancer invasion and angiogenesis. Aberrant expression of DP4 and FAP is associated with numerous cancers, including breast and epithelial ovarian carcinoma. We investigated the mRNA levels, protein expression and enzyme activity of the structural homologs DP8 and DP9, in addition to DP4 and FAP, in three breast carcinoma (MDA-MB-231, MDA-MB-453, MCF-7), three epithelial ovarian carcinoma (EOC) (OVCA-432, OVCA-429, SKOV3), 293T and HeLa cell lines. In addition, DP2 and prolyl endopeptidase (PEP) mRNA and enzyme levels were measured and compared in each cell line. Ubiquitous but differential expression of DP8 and DP9 mRNA and protein was observed across all cell lines. Relative to EOC, DP8 protein was lower in the breast carcinoma cell lines (p= 0.057), suggesting that DP8 may play differing roles in different cancer cell types. A strong, negative, non-reciprocal relationship was identified between DP9 protein and DP4 mRNA (r=-0.903, p=0.002) and protein (r=-0.810, p=0.015). This suggests that DP4 expression plays an important role in the post-transcriptional regulation of DP9 in breast and ovarian cancer cell lines. Overall, this study suggests a potential role for DP8 and DP9 in breast and ovarian cancer and further investigations in this area are required. IntroductionBreast and ovarian cancer are two of the most common and lethal cancers affecting women worldwide. Estimates rank breast cancer as being the number one cause of new cancer cases (1,383,000 cases, 22.9%) and cancer related deaths (458,000 deaths, 13.7%) in women worldwide in 2008. Ovarian cancer was ranked as the seventh cause of new cancer cases (225,000 cases, 3.7%) and cancer related deaths (140,000 deaths, 4.2%) in women worldwide in the same year (1). Among gynecological malignancies, epithelial ovarian carcinoma (EOC) is the most lethal to women in the world, accounting for approximately 90% of all tumors affecting the ovaries (2). Mortality from breast cancer often results from distant metastatic spread to lung, bone and lymph node tissue while diagnosis of EOC typically occurs in the late stages of disease after its spread into the peritoneal cavity or other distant sites (2), thus making it difficult for effective treatment to be administered. Although a number of risk factors for the development of breast and ovarian cancer have been identified the exact origin and pathogenesis of disease is still poorly understood (3,4). Increasing our knowledge about the fundamental biology of these diseases is needed for the development of improved diagnostic, prognostic and therapeutic interventions at all stages of disease.Enzymatic members of the DP4-like gene family, DP4, FAP, DP8 and DP9, share the rare ability to cleave N-terminal dipeptides at post-proline bonds in the penultimate position and play an important role in the biological processing of the N-termini of peptides such as chemokines, glu...

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“…31 C6 tumor model which is FAPα negative was also generated as a control. Western blot results confirm that FAPα is indeed expressed in U87MG tumor but not in C6 tumor (Figure 3).…”

Section: Discussionmentioning

confidence: 99%

Activatable Near-Infrared Fluorescent Probe for In Vivo Imaging of Fibroblast Activation Protein-alpha

Chen

Liu

et al. 2012

Bioconjugate Chem.

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Fibroblast activation protein-alpha (FAPα) is a cell surface glycoprotein which is selectively expressed by tumor-associated fibroblasts in malignant tumors but rarely on normal tissues. FAPα has also been reported to promote tumor growth and invasion and therefore has been of increasing interest as a promising target for designing tumor-targeted drugs and imaging agents. Although medicinal study on FAPα inhibitors has led to the discovery of many FAPα-targeting inhibitors including a drug candidate in a phase II clinical trial, the development of imaging probes to monitor the expression and activity of FAPα in vivo has largely lagged behind. Herein we report an activatable near infrared (NIR) fluorescent probe (ANPFAP) for in vivo optical imaging of FAPα. The ANPFAP consists of a NIR dye (Cy5.5) and a quencher dye (QSY21) which are linked together by a short peptide sequence (KGPGPNQC) specific for FAPα cleavage. Because of the efficient fluorescence resonance energy transfer (FRET) between Cy5.5 and QSY21 in ANPFAP, high contrast on the NIR fluorescence signal can be achieved after the cleavage of the peptide sequence by FAPα both in vitro and in vivo. In vitro assay on ANPFAP indicated the specificity of the probe to FAPα. The in vivo optical imaging using ANPFAP showed fast tumor uptake as well as high tumor to background contrast on U87MG tumor models with FAPα expression, while much lower signal and tumor contrast were observed in the C6 tumor without FAPα expression, demonstrating the in vivo targeting specificity of the ANPFAP. Ex vivo imaging also demonstrated ANPFAP had high tumor uptake at 4 h post injection. Collectively, these results indicated that ANPFAP could serve as a useful NIR optical probe for early detection of FAPα expressing tumors.

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Coupled expression of dipeptidyl peptidase-IV and fibroblast activation protein-α in transformed astrocytic cells

Cited by 18 publications

References 20 publications

Heterogeneity of molecular forms of dipeptidyl peptidase-IV and fibroblast activation protein in human glioblastomas

Heterogeneity of molecular forms of dipeptidyl peptidase-IV and fibroblast activation protein in human glioblastomas

Expression profiling of dipeptidyl peptidase 8 and 9 in breast and ovarian carcinoma cell lines

Activatable Near-Infrared Fluorescent Probe for In Vivo Imaging of Fibroblast Activation Protein-alpha

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