Overexpression of CD26/DPPIV in mesothelioma tissue and mesothelioma cell lines

Amatya, Vishwa Jeet; Takeshima, Yukio; Kushitani, Kei; Yamada, Taketo; Morimoto, Chikao; Inai, Kei

doi:10.3892/or.2011.1449

Cited by 19 publications

(33 citation statements)

References 32 publications

(28 reference statements)

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“…Similar to sMET, sCD26 originates from the shedding of surface-bound CD26. Overexpression of DPP4 is observed in various human cancers, including thyroid, breast, prostate, and ovarian cancers and is involved in tumor development, invasion, and metastasis (60,61). However, previous studies have also observed that sCD26 was deficient in total homogenates of colon, kidney, lung, and liver tumors (62,63) as well as in different transformed and cancer-derived cell lines (64).…”

Section: Discussionmentioning

confidence: 94%

In-depth Proteomic Analysis of Six Types of Exudative Pleural Effusions for Nonsmall Cell Lung Cancer Biomarker Discovery

Liu

Chen

Wang³

et al. 2015

Molecular & Cellular Proteomics

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Pleural effusion (PE), a tumor-proximal body fluid, may be a promising source for biomarker discovery in human cancers. Because a variety of pathological conditions can lead to PE, characterization of the relative PE proteomic profiles from different types of PEs would accelerate discovery of potential PE biomarkers specifically used to diagnose pulmonary disorders. Using quantitative proteomic approaches, we identified 772 nonredundant proteins from six types of exudative PEs, including three malignant PEs (MPE, from lung, breast, and gastric cancers), one lung cancer paramalignant PE, and two benign diseases (tuberculosis and pneumonia). Spectral counting was utilized to semiquantify PE protein levels. Principal component analysis, hierarchical clustering, and Gene Ontology of cellular process analyses revealed differential levels and functional profiling of proteins in each type of PE. We identified 30 candidate proteins with twofold higher levels (q<0.05) in lung cancer MPEs than in the two benign PEs. Three potential markers, MET, DPP4, and PTPRF, were further verified by ELISA using 345 PE samples. The protein levels of these potential biomarkers were significantly higher in lung cancer MPE than in benign diseases or lung cancer paramalignant PE. The area under the receiver-operator characteristic curve for three combined biomarkers in discriminating lung cancer MPE from benign diseases was 0.903. We also observed that the PE protein levels were more clearly discriminated in effusions in which the cytological examination was positive and that they would be useful in rescuing the false negative of cytological examination in diagnosis of nonsmall cell lung cancer-MPE. Western blotting analysis further demonstrated that MET overexpression in lung cancer cells would contribute to the elevation of soluble MET in MPE. Our results collectively demonstrate the utility of label-free quantitative proteomic approaches in establishing differential PE proteomes and provide a new database of proteins that can be used to facilitate identification of pulmonary disorder-related biomarkers. Molecular & Cellular Proteomics

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Section: Discussionmentioning

confidence: 94%

In-depth Proteomic Analysis of Six Types of Exudative Pleural Effusions for Nonsmall Cell Lung Cancer Biomarker Discovery

Liu

Chen

Wang³

et al. 2015

Molecular & Cellular Proteomics

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“…JMN cells (biphasic) were a kind gift from Dr Brenda Gerwin (Laboratory of Human Carcinogenesis, National Institutes of Health, Bethesda, MD, USA). Malignant pleural mesothelioma or HEK293 cells were cultured by the methods previously described (Inamoto et al , 2007; Amatya et al , 2011). MSTO-P cells were transfected with a full-length CD26 (CD26WT) or CD26-CD10 chimaeric receptor (CD26/10Chi) subcloned retroviral shuttle plasmid pLNCX2 vector (Clontech Laboratories Inc., Mountain View, CA, USA) using the Lipofectamine2000 reagent (Life Technologies Inc., Carlsbad, CA, USA).…”

Section: Methodsmentioning

confidence: 99%

Regulation of somatostatin receptor 4-mediated cytostatic effects by CD26 in malignant pleural mesothelioma

et al. 2014

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Background:Malignant pleural mesothelioma (MPM) is an aggressive neoplasm arising from mesothelial lining of pleura. CD26 molecules preferentially expressed on epithelioid type of MPM. This study investigates the molecular mechanisms of CD26 regulating MPM cells in vitro and in vivo.Methods:Biochemical and cell biological approaches were used for identifying a novel molecular target of MPM. Its contribution to tumour expansion has been also assessed using animal models. The clinical samples of MPM were also assessed for its expression.Results:We identify that cytostatic effects in MPM are mediated by somatostatin (SST) receptor 4 (SSTR4), being inhibited by the interaction of CD26 molecules. We also indicates that SSTR4-mediated cytostatic effects are regulated by SHP-2 PTP, and that this inhibitory effect by SST agonist is enhanced via lipid raft clustering of associated molecules following crosslinking of anti-CD26 antibody. Finally, using an in vivo xenograft model, we demonstrate that the anti-tumour effect of anti-CD26 mAb is enhanced when combined with SSTR4 agonist treatment, and that SSTR4 is highly coexpressed with CD26 on epithelioid or biphasic types of MPM tissues obtained from patients' surgical specimens.Conclusions:Combination therapy with humanised anti-CD26 mAb and SSTR4 agonist may therefore potentiate anti-tumour effect on MPM.

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“…More recently, we showed that CD26 is preferentially expressed on malignant mesothelioma cells but not on normal mesothelial cells, and suggested that membranous expression of CD26 indicates an importance in treatment of patients with MPM (19). More importantly, humanized anti-CD26 antibody inhibited growth of malignant mesothelioma cells and induced long-term survival of tumortransplanted severe combined immunodeficient mice (20).…”

Section: Introductionmentioning

confidence: 96%

“…Amatya and Y. Takeshima). Though cytoplasmic expression of CD26 was observed in many of the tumor cells in most of the cases, CD26 expression in mesothelioma was based on its membranous expression (19). In detail, it was scored as 0, absence of membranous expression on tumor cells; þ1, membranous expression on up to 25% of tumor cells; þ2, membranous expression on 26% to 50% of tumor cells; and þ3, membranous expression on more than 50% of tumor cells.…”

Section: Immunohistochemical Stainingmentioning

confidence: 99%

“…For this purpose, we used CD26-KD cells as generated above. Moreover, we used CD26-overexpressed MM cells (CD26-Trf) generated with retroviral transfection of human CD26 into CD26-negative MSTO-211H (MSTO) cells (19). Total RNA was extracted from these cells using standardized protocols of conventional published methodology (RNeasy; QIAGEN).…”

Section: Microarray Data Generationmentioning

confidence: 99%

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CD26 Overexpression Is Associated with Prolonged Survival and Enhanced Chemosensitivity in Malignant Pleural Mesothelioma

Aoe

Amatya

Fujimoto

et al. 2012

Clinical Cancer Research

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Purpose: Malignant pleural mesothelioma (MPM) is an aggressive and therapy-resistant neoplasm arising from the pleural mesothelial cells, without established indicators to predict responsiveness to chemotherapy.Experimental Design: Our study involving 79 MPM patients showed that 73.4% of MPM expressed CD26 on cell membrane.Results: The majority of epithelioid and biphasic types of MPM expressed CD26 on the cell membrane, whereas the sarcomatoid type showed a lack of CD26 surface expression. Although the sarcomatoid type was associated with poor prognosis (P < 0.0001), no significant relationship between CD26 expression and survival was observed. On the contrary, there was a trend for an association between response rate to chemotherapy and CD26 expression (P ¼ 0.053), with a higher level of CD26 expression more likely to be linked to better response to chemotherapy. Moreover, CD26 expression was a significant factor associated with improved survival in patients who received chemotherapy [median survival time (MST), 18.6 vs. 10.7 months, P ¼ 0.0083]. Furthermore, CD26 expression was significantly associated with better prognosis in patients receiving non-pemetrexed-containing regimens (MST, 14.2 vs. 7.4 months, P ¼ 0.0042), whereas there was no significant association between CD26 expression and survival time for patients receiving pemetrexed-containing regimens. Our in vitro and microarray studies showed that mesothelioma cells expressing high CD26 displayed high proliferative activity, and CD26 expression was closely linked to cell-cycle regulation, apoptosis, and chemotherapy resistance.Conclusions: Our results strongly suggest that CD26 is a clinically significant biomarker for predicting response to chemotherapy for MPM.

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Overexpression of CD26/DPPIV in mesothelioma tissue and mesothelioma cell lines

Cited by 19 publications

References 32 publications

In-depth Proteomic Analysis of Six Types of Exudative Pleural Effusions for Nonsmall Cell Lung Cancer Biomarker Discovery

In-depth Proteomic Analysis of Six Types of Exudative Pleural Effusions for Nonsmall Cell Lung Cancer Biomarker Discovery

Regulation of somatostatin receptor 4-mediated cytostatic effects by CD26 in malignant pleural mesothelioma

CD26 Overexpression Is Associated with Prolonged Survival and Enhanced Chemosensitivity in Malignant Pleural Mesothelioma

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