CD26/dipeptidyl peptidase IV enhances expression of topoisomerase II alpha and sensitivity to apoptosis induced by topoisomerase II inhibitors

Sato, Kazuya; Aytac, Ugur; Yamochi, Tadanori; Ohnuma, Kei; McKee, Kathryn S.; Morimoto, Chikao; Dang, Nam H.

doi:10.1038/sj.bjc.6601253

Cited by 22 publications

(19 citation statements)

References 37 publications

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“…We showed previously that transfectional overexpression of CD26 results in the up-regulation of topoisomerase IIa expression, associated with enhanced sensitivity to the topoisomerase II inhibitor doxorubicin (12,(15)(16)(17). Consistent with our earlier work, our present studies clearly show that CD26 depletion results in decreased doxorubicin sensitivity (Fig.…”

Section: Resultsmentioning

confidence: 99%

CD26 Regulates p38 Mitogen-Activated Protein Kinase–Dependent Phosphorylation of Integrin β1, Adhesion to Extracellular Matrix, and Tumorigenicity of T-Anaplastic Large Cell Lymphoma Karpas 299

et al. 2005

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CD26 is an antigen with key role in T-cell biology and is expressed on selected subsets of aggressive T-cell malignancies. To elucidate the role of CD26 in tumor behavior, we examine the effect of CD26 depletion by small interfering RNA transfection of T-anaplastic large cell lymphoma Karpas 299. We show that the resultant CD26-depleted clones lose the ability to adhere to fibronectin and collagen I. Because antiintegrin B 1 blocking antibodies also prevent binding of Karpas 299 to fibronectin and collagen I, we then evaluate the CD26-integrin B 1 association. CD26 depletion does not decrease integrin B 1 expression but leads to dephosphorylation of both integrin B 1 and p38 mitogen-activated protein kinase (MAPK). Moreover, our data showing that the p38MAPK inhibitor SB203580 dephosphorylates integrin B 1 and that binding of the anti-CD26 antibody 202.36 dephosphorylates both p38MAPK and integrin B 1 on Karpas 299, leading to loss of cell adhesion to the extracellular matrix, indicate that CD26 mediates cell adhesion through p38MAPK-dependent phosphorylation of integrin B 1 . Finally, in vivo experiments show that depletion of CD26 is associated with loss of tumorigenicity and greater survival. Our findings hence suggest that CD26 plays an important role in tumor development and may be a novel therapeutic target for selected neoplasms. (Cancer Res 2005; 65(15): 6950-6)

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Section: Resultsmentioning

confidence: 99%

CD26 Regulates p38 Mitogen-Activated Protein Kinase–Dependent Phosphorylation of Integrin β1, Adhesion to Extracellular Matrix, and Tumorigenicity of T-Anaplastic Large Cell Lymphoma Karpas 299

et al. 2005

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“…17 DPP IV has been shown to participate in T-cell biology as a co-stimulatory molecule able to regulate signalling transduction pathways. [18][19][20] In addition to its role in T-cell biology, DPP IV also plays an important role in the pathogenesis of kidney diseases such as IgA nephropathy. 21 We here studied the excretion of DPP IV in urinary microvesicles in a small cohort of patients with T2DM by categorising them into three groups according to the severity of kidney damage.…”

Section: Discussionmentioning

confidence: 99%

Dipeptidyl peptidase-IV is a potential molecular biomarker in diabetic kidney disease

Sun

Deng

Guan

et al. 2012

Diabetes and Vascular Disease Research

117

113

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The present study was designed to identify the changes in microvesicle-dipeptidyl peptidase-IV (DPP IV) levels in human urine and serum, and to determine whether there were correlations with the severity of diabetic kidney disease (DKD). A total of 127 patients with type 2 diabetes mellitus (T2DM) were divided into three groups according to the urinary albumin/ creatinine ratio (UACR): microalbuminuria group (n = 50); macroalbuminuria group (n = 34) and normoalbuminuria group (n = 43), and 34 age-and sex-matched non-diabetic healthy subjects were selected as controls. Microvesicle-bound DPP IV and free urinary DPP IV were separated by a filtra-centrifugation method. The total microvesicles were captured by a specific monoclonal antibody, AD-1. DPP IV activity was determined by measuring the cleavage of chromogenic free 4-nitroaniline from Gly-Pro-p-nitroanilide at 405 nm with an ELISA plate reader. DPP IV protein levels were determined by ELISA and Western blot. Our results showed that the microvesicle-bound type was the major form of DPP IV in urine; the urinary microvesicle-DPP IV excretion of each T2DM group was significantly higher compared with controls. The urinary microvesicle-DPP IV level was positively correlated with UACR in patients with T2DM. These findings suggest that the urinary level of microvesicle-bound DPP IV is associated with the severity of DKD.

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“…Preparation of whole-cell lysates, cell fractionations, and SDS-PAGE were done as described elsewhere (23).…”

Section: Methodsmentioning

confidence: 99%

Humanized Anti-CD26 Monoclonal Antibody as a Treatment for Malignant Mesothelioma Tumors

Inamoto

Yamada

Ohnuma

et al. 2007

Clinical Cancer Research

111

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Purpose: CD26 is a 110-kDa cell surface antigen with a role in tumor development. In this report, we show that CD26 is highly expressed on the cell surface of malignant mesothelioma and that a newly developed humanized anti-CD26 monoclonal antibody (mAb) has an inhibitory effect on malignant mesothelioma cells in both in vitro and in vivo experiments. Experimental Design: Using immunohistochemistry, 12 patients' surgical specimens consisting of seven malignant mesothelioma, three reactive mesothelial cells, and two adenomatoid tumors were evaluated for expression of CD26. The effects of CD26 on malignant mesothelioma cells were assessed in the presence of transfection of CD26-expressing plasmid, humanized anti-CD26 mAb, or small interfering RNA against CD26. The in vivo growth inhibitory effect of humanized anti-CD26 mAb was assessed in human malignant mesothelioma cell mouse xenograft models. Results: In surgical specimens, CD26 is highly expressed in malignant mesothelioma but not in benign mesothelial tissues. Depletion of CD26 by small interfering RNA results in the loss of adhesive property, suggesting that CD26 is a binding protein to the extracellular matrix. Moreover, our in vitro data indicate that humanized anti-CD26 mAb induces cell lysis of malignant mesothelioma cells via antibody-dependent cell-mediated cytotoxicity in addition to its direct anti-tumor effect via p27 kip1 accumulation. In vivo experiments with mouse xenograft models involving human malignant mesothelioma cells show that humanized anti-CD26 mAb treatment drastically inhibits tumor growth in tumor-bearing mice, resulting in enhanced survival. Conclusions: Our data strongly suggest that humanized anti-CD26 mAb treatment may have potential clinical use as a novel cancer therapeutic agent in CD26-positive malignant mesothelioma.

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CD26/dipeptidyl peptidase IV enhances expression of topoisomerase II alpha and sensitivity to apoptosis induced by topoisomerase II inhibitors

Cited by 22 publications

References 37 publications

CD26 Regulates p38 Mitogen-Activated Protein Kinase–Dependent Phosphorylation of Integrin β1, Adhesion to Extracellular Matrix, and Tumorigenicity of T-Anaplastic Large Cell Lymphoma Karpas 299

CD26 Regulates p38 Mitogen-Activated Protein Kinase–Dependent Phosphorylation of Integrin β1, Adhesion to Extracellular Matrix, and Tumorigenicity of T-Anaplastic Large Cell Lymphoma Karpas 299

Dipeptidyl peptidase-IV is a potential molecular biomarker in diabetic kidney disease

Humanized Anti-CD26 Monoclonal Antibody as a Treatment for Malignant Mesothelioma Tumors

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