CD26/DPPIV cell membrane expression and DPPIV activity in plasma of patients with acute leukemia

Andrade, Camilla F C G de; Bigni, Ricardo; Pombo‐de‐Oliveira, Maria S.; Alves, Gilda; Pereira, Denise A.

doi:10.1080/14756360802334800

Cited by 16 publications

(7 citation statements)

References 29 publications

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“…In contrast, DPP4 also appears to have an important role in the development of selected haematological malignancies (Farag et al ., ). Higher levels of DPP4 are expressed in chronic lymphocytic leukaemia B cells compared with their normal resting B cell counterparts (de Andrade et al ., ). In addition, DPP4 expression is mainly found in aggressive subtypes of non‐Hodgkin lymphoma, such as T cell lymphoblastic lymphoma (T‐LBL)/T cell acute lymphoblastic leukaemia (T‐ALL) and T cell CD30+ anaplastic large cell lymphoma (Ribatti et al ., ).…”

Section: Discussionmentioning

confidence: 97%

Dipeptidyl peptidase 4 promotes epithelial cell transformation and breast tumourigenesis via induction of PIN1 gene expression

Choi

Lim

et al. 2015

British J Pharmacology

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BACKGROUND AND PURPOSEDipeptidyl peptidase 4 (DPP4) is an aminopeptidase that is widely expressed in different cell types. Recent studies suggested that DPP4 plays an important role in tumour progression in several human malignancies. Here we have examined the mechanisms by which up-regulation of DPP4 expression causes epithelial transformation and mammary tumourigenesis. EXPERIMENTAL APPROACHExpression of DPP4 and the peptidylprolyl cis/trans isomerase, NIMA-interacting 1 (PIN1), and the cytotoxic effects of combined treatment with sitagliptin and juglone were investigated by immunohistochemistry, immunoblotting, real-time PCR, TUNEL and soft agar assays, using MCF7 cells. The effects of sitagliptin on tumour development in vivo were studied in the syngeneic 4T1 metastatic breast cancer model. KEY RESULTSActivity of the transcription factor E2F1 induced by EGF was enhanced by DPP4, thus increasing PIN1 expression. Furthermore, DPP4 enhanced MEK/ERK and JNK/c-Jun signalling induced by EGF, inducing AP-1 activity and epithelial cell transformation. In contrast, DPP4 silencing or DPP4 inhibition in MCF7 cells inhibited PIN1 expression via E2F1 activity induced by EGF, decreasing colony formation and inducing DNA fragmentation. In the syngeneic 4T1 metastatic breast cancer model, DPP4 overexpression increased tumour development, whereas treatment with sitagliptin and/or juglone suppressed it. Consistent with these observations, DPP4 levels were positively correlated with PIN1 expression in human breast cancer. CONCLUSIONS AND IMPLICATIONSDPP4 promoted EGF-induced epithelial cell transformation and mammary tumourigenesis via induction of PIN1 expression, suggesting that sitagliptin targeting of DPP4 could be a treatment strategy in patients with breast cancer. AbbreviationsAP-1, activator protein-1; DPP-4, dipeptidyl peptidase 4; GLP-1, glucagon-like peptide-1; MTT, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide; T-LBL, T cell lymphoblastic leukaemia; T-ALL, T cell acute lymphoblastic leukaemia; T2DM, type 2 diabetes mellitus BJP British Journal of Pharmacology

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Section: Discussionmentioning

confidence: 97%

Dipeptidyl peptidase 4 promotes epithelial cell transformation and breast tumourigenesis via induction of PIN1 gene expression

Choi

Lim

et al. 2015

British J Pharmacology

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“…Patients with B-cell chronic lymphocytic leukemia had elevated mRNA and protein levels of DPP8 and DPP9; 35 plasma DPP activity was elevated in 80 and 62% in patients with lymphoid leukemia and AML, respectively. 36 These elevated DPP levels suggest these enzymes may have a role in leukemia pathogenesis, and are thus valuable therapeutic targets.…”

Section: Discussionmentioning

confidence: 99%

Inhibition of intracellular dipeptidyl peptidases 8 and 9 enhances parthenolide’s anti-leukemic activity

et al. 2013

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Parthenolide is selectively toxic to leukemia cells; however, it also activates cell protective responses that may limit its clinical application. Therefore, we sought to identify agents that synergistically enhance parthenolide's cytotoxicity. Using a high-throughput combination drug screen, we identified the anti-hyperglycemic, vildagliptin, which synergized with parthenolide to induce death of the leukemia stem cell line, TEX (combination index (CI)=0.36 and 0.16, at effective concentration (EC) 50 and 80, respectively; where CI <1 denotes statistical synergy). The combination of parthenolide and vildagliptin reduced the viability and clonogenic growth of cells from acute myeloid leukemia patients and had limited effects on the viability of normal human peripheral blood stem cells. The basis for synergy was independent of vildagliptin's primary action as an inhibitor of dipeptidyl peptidase (DPP) IV. Rather, using chemical and genetic approaches we demonstrated that the synergy was due to inhibition of the related enzymes DPP8 and DPP9. In summary, these results highlight DPP8 and DPP9 inhibition as a novel chemosensitizing strategy in leukemia cells. Moreover, these results suggest that the combination of vildagliptin and parthenolide could be useful for the treatment of leukemia.

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“…Studies have suggested that CD26 plays a regulatory role in the neoplastic transformation and progression of various types of tumours, and it may also play a role in tumour migration and metastasis as a result of its ability to bind extracellular matrix proteins [1,2]. It is thought that CD26 plays an important role in hematological malignancies, mainly in aggressive subtypes of T-cell non-Hodgkin lymphoma in which it is highly expressed by neoplastic cells [3,4]. Although CD26 expression is very low in B-cells, it is greatly up regulated following activation [5].…”

Section: Introductionmentioning

confidence: 99%

CD26 Expression in Mature B-cell Neoplasms and its Prognostic Impact on B-Cell Chronic Lymphocytic Leukemia

Ghannam¹,

Taalab²,

Ghazy³

et al. 2014

J Blood Disord Transfus

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The study was based on 58 (40 males, 18 females) consecutive, previously untreated CLL, 7 HCL (5 males, 2 females), 23 CD5 negative LPD (15 males, 8 females) and 12 multiple myeloma (8 males, 4 females). Mean age of CLL, HCL, CD5 negative LPD and multiple Abstract CD26/dipeptidyl peptidase IV (DPPIV) is a multifunctional membrane protein and it is strongly upregulated in activated B-cells. We aimed to evaluate CD26 expression in mature B cell neoplasms, and its prognostic role in B cell chronic lymphocytic leukaemias (B-CLL). CD26 expression was evaluated by flow cytometry in various B cell neoplasms. CD26 expression was high in MMs and HCLs, variable in B-CLLs and in CD5neg B-CLPDs. Kaplan-Meier curves revealed a significantly shorter progression free survival (PFS), and lymphocytic doubling time (LDT) in the CD26 high expression group (p=0.014, 0.024 respectively). High CD26, CD38 and/or ZAP70 showed significantly shorter PFS, (p=0.020, 0.022 respectively) and LDT (p=0.024, 0.024 respectively) when compared to both low expression CD26, CD38 and/or ZAP70. CD26 expression may identify subsets of B-CLL patients with an unfavorable clinical outcome, thus suggesting its potential role as a marker in a future routine cytofluorimetric panel for B-CLLs.

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CD26/DPPIV cell membrane expression and DPPIV activity in plasma of patients with acute leukemia

Cited by 16 publications

References 29 publications

Dipeptidyl peptidase 4 promotes epithelial cell transformation and breast tumourigenesis via induction of PIN1 gene expression

Dipeptidyl peptidase 4 promotes epithelial cell transformation and breast tumourigenesis via induction of PIN1 gene expression

Inhibition of intracellular dipeptidyl peptidases 8 and 9 enhances parthenolide’s anti-leukemic activity

CD26 Expression in Mature B-cell Neoplasms and its Prognostic Impact on B-Cell Chronic Lymphocytic Leukemia

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