Dipeptidyl Peptidase-IV and Related Proteases in Brain Tumors

Bušek, Petr; Šedo, Aleksi

doi:10.5772/53888

Cited by 5 publications

(2 citation statements)

References 232 publications

(299 reference statements)

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“…[A,B]. Based on: (A) https://www.lgcstandards-atcc.org/; (B) https://www.phe-culturecollections.org.uk/; (C) [93]; (D) [94]; (E) [95]; (F) [96]; (G) [97]; (H) [98]; (I) [99]; (J) [100]; (K) [101]; (L) [102]; (M) [103]; (N) [104]; (O) [105]; (P) [106]; (Q) [107]; (R) [108]; (S) [109]; (T) [110]; (U) [111]; (V)[112]; (W)[113]; (X)[114]; (Y)[115]; (Z)[116]; (Aa)[117]; (Bb)[118]; (Cc)[119]; (Dd)[120]; (Ee)[121]; (Ff)[122]; (Gg)[70]; Hh)[123]; (Ii)[124]; (Jj)[125]; (Kk)[126] …”

mentioning

confidence: 99%

Considering the Experimental Use of Temozolomide in Glioblastoma Research

Herbener¹,

Burster

Goreth³

et al. 2020

Biomedicines

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Temozolomide (TMZ) currently remains the only chemotherapeutic component in the approved treatment scheme for Glioblastoma (GB), the most common primary brain tumour with a dismal patient’s survival prognosis of only ~15 months. While frequently described as an alkylating agent that causes DNA damage and thus—ultimately—cell death, a recent debate has been initiated to re-evaluate the therapeutic role of TMZ in GB. Here, we discuss the experimental use of TMZ and highlight how it differs from its clinical role. Four areas could be identified in which the experimental data is particularly limited in its translational potential: 1. transferring clinical dosing and scheduling to an experimental system and vice versa; 2. the different use of (non-inert) solvent in clinic and laboratory; 3. the limitations of established GB cell lines which only poorly mimic GB tumours; and 4. the limitations of animal models lacking an immune response. Discussing these limitations in a broader biomedical context, we offer suggestions as to how to improve transferability of data. Finally, we highlight an underexplored function of TMZ in modulating the immune system, as an example of where the aforementioned limitations impede the progression of our knowledge.

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confidence: 99%

Considering the Experimental Use of Temozolomide in Glioblastoma Research

Herbener¹,

Burster

Goreth³

et al. 2020

Biomedicines

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“…The dipeptidyl peptidase (DPP)-4 inhibitor increases glucagon-like peptide (GIP-1) and promotes insulin secretion in type 2 diabetic patients [5]. However, DPP-4 cleaves many growth factors, chemokines and neuropeptides that may promote human malignancies, and DPP-4 inhibitors potentially increase these substances [6][7][8][9].…”

Section: Introductionmentioning

confidence: 99%

Deficiency in Dipeptidyl Peptidase-4 Promotes Chemoresistance Through the CXCL12/CXCR4/mTOR/TGFβ Signaling Pathway in Breast Cancer Cells

Yang

Kumagai

et al. 2020

IJMS

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Dipeptidyl peptidase (DPP)-4, a molecular target of DPP-4 inhibitors, which are type 2 diabetes drugs, is expressed in a variety of cell types, tissues and organs. DPP-4 has been shown to be involved in cancer biology, and we have recently shown that a DPP-4 inhibitor promoted the epithelial mesenchymal transition (EMT) in breast cancer cells. The EMT is known to associate with chemotherapy resistance via the induction of ATP-binding cassette (ABC) transporters in cancer cells. Here, we demonstrated that deficiency in DPP-4 promoted chemotherapy resistance via the CXCL12/CXCR4/mTOR axis, activating the TGFβ signaling pathway via the expression of ABC transporters. DPP-4 inhibition enhanced ABC transporters in vivo and in vitro. Doxorubicin (DOX) further induced ABC transporters in DPP-4-deficient 4T1 cells, and the induction of ABC transporters was suppressed by either the CXCR4 inhibitor AMD3100, the mTOR inhibitor rapamycin or a neutralizing TGFβ (1, 2 and 3) antibody(N-TGFβ). Knockdown of snail, an EMT-inducible transcription factor, suppressed ABC transporter levels in DOX-treated DPP-4-deficient 4T1 cells. In an allograft mouse model, however, the effects of DOX in either primary tumor or metastasis were not statistically different between control and DPP-4-kd 4T1. Taken together, our findings suggest that DPP-4 inhibitors potentiate chemotherapy resistance via the induction of ABC transporters by the CXCL12/CXCR4/mTOR/TGFβ signaling pathway in breast cancer cells.

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Co-expression of the homologous proteases fibroblast activation protein and dipeptidyl peptidase-IV in the adult human Langerhans islets

Bušek

Hrabal

Frič

et al. 2014

Histochem Cell Biol

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Fibroblast activation protein (FAP, seprase, EC 3.4.21.B28) and dipeptidyl peptidase-IV (DPP-IV, CD26, EC 3.4.14.5) are homologous serine proteases implicated in the modulation of the bioavailability and thus the function of a number of biologically active peptides. In spite of their generally nonoverlapping expression patterns, DPP-IV and FAP are co-expressed and probably co-regulated in certain cell types suggesting that for some biological processes their functional synergy is essential. By an in situ enzymatic activity assay, we show an abundant DPP-IV-like enzymatic activity sensitive to a highly specific DPP-IV inhibitor sitagliptin and corresponding DPP-IV immunoreactivity in the adult human islets of Langerhans. Moreover, the homologous protease FAP was present in the human endocrine pancreas and was co-expressed with DPP-IV. DPP-IV and FAP were found in the pancreatic alpha cells as determined by the co-localization with glucagon immunoreactivity. In summary, we show abundant enzymatic activity of the canonical DPP-IV (CD26) in Langerhans islets in the natural tissue context and demonstrate for the first time the co-expression of FAP and DPP-IV in pancreatic alpha cells in adult humans. Given their ability to proteolytically modify several biologically active peptides, both proteases have the potential to modulate the paracrine signaling in the human Langerhans islets.

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Dipeptidyl Peptidase-IV and Related Proteases in Brain Tumors

Cited by 5 publications

References 232 publications

Considering the Experimental Use of Temozolomide in Glioblastoma Research

Considering the Experimental Use of Temozolomide in Glioblastoma Research

Deficiency in Dipeptidyl Peptidase-4 Promotes Chemoresistance Through the CXCL12/CXCR4/mTOR/TGFβ Signaling Pathway in Breast Cancer Cells

Co-expression of the homologous proteases fibroblast activation protein and dipeptidyl peptidase-IV in the adult human Langerhans islets

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