ANGPTL2 expression in gastric cancer tissues and cells and its biological behavior

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Abstract

AIM

To explore expression of angiopoietin-like protein 2 (ANGPTL2) and its effect on biological behavior such as proliferation and invasiveness in gastric cancer.

METHODS

Western blotting was used to detect expression of ANGPTL2 in 60 human normal gastric tissues, 60 human gastric cancer tissues and gastric cell lines including GES-1, N87, SGC7901, BGC823 and PAMC82. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and Transwell assay were used to detect the proliferation and invasive ability of gastric cancer cells.

RESULTS

Compared to normal tissues, ANGPTL2 protein levels were significantly upregulated in gastric tissues, and this level was closely correlated with gastric tumor grade, clinical stage and lymph node metastasis. Compared to GES-1 cells, ANGPTL2 mRNA and protein levels were significantly increased in gastric cancer cells including N87, SGC7901, BGC823 and PAMC82. The expression of ANGPTL2 in highly malignant gastric cancer cell lines BGC823 and PAMC82 was significantly higher than in low malignancy gastric cancer cell lines N87 and SGC7901. MTT and Transwell experiments indicated that the proliferation rate and invasive ability of stable overexpressed gastric cancer cells was faster than in cells transfected with Lv-NC and blank control cells, and the invasive ability of stable overexpressed gastric cancer cells was higher than that of cells transfected with Lv-NC and blank control cells.

CONCLUSION

ANGPTL2 contributed to proliferation and invasion of gastric cancer cells. In clinical treatment, ANGPTL2 may become a new target for treatment of gastric cancer.

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Most cited references 37

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Gastric cancer and the epoch of immunotherapy approaches.

Elena Niccolai, Antonio Taddei, Domenico Prisco … (2015)

The incidence of gastric cancer (GC) fell dramatically over the last 50 years, but according to IARC-Globocan 2008, it is the third most frequent cause of cancer-related deaths with a case fatality GC ratio higher than other common malignancies. Surgical resection is the primary curative treatment for GC though the overall 5-year survival rate remains poor (approximately 20%-25%). To improve the outcome of resectable gastric cancer, different treatment strategies have been evaluated such as adjuvant or perioperative chemotherapy. In resected gastric cancer, the addition of radiotherapy to chemotherapy does not appear to provide any additional benefit. Moreover, in metastatic patients, chemotherapy is the mainstay of palliative therapy with a median overall survival of 8-10 mo and objective response rates of merely 20%-40%. Therefore, the potential for making key beneficial progress is to investigate the GC molecular biology to realize innovative therapeutic strategies, such as specific immunotherapy. In this review, we provide a panoramic view of the different immune-based strategies used for gastric cancer treatment and the results obtained in the most significant clinical trials. In detail, firstly we describe the therapeutic approaches that utilize the monoclonal antibodies while in the second part we analyze the cell-based immunotherapies.

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Macrophage-derived angiopoietin-like protein 2 accelerates development of abdominal aortic aneurysm.

Hirokazu Tazume, Keishi Miyata, Zhe Tian … (2012)

Recently, we reported that angiopoietin-like protein 2 (Angptl2) functions in various chronic inflammatory diseases. In the present study, we asked whether Angptl2 and its associated chronic inflammation contribute to abdominal aortic aneurysm (AAA). Immunohistochemistry revealed that Angptl2 is abundantly expressed in infiltrating macrophages within the vessel wall of patients with AAA and in a CaCl(2)-induced AAA mouse model. When Angptl2-deficient mice were used in the mouse model, they showed decreased AAA development compared with wild-type mice, as evidenced by reduction in aneurysmal size, less severe destruction of vessel structure, and lower expression of proinflammatory cytokines and matrix metalloproteinase-9. However, no difference in the number of infiltrating macrophages within the aortic aneurysmal vessel wall was observed between genotypes. AAA development was also significantly suppressed in wild-type mice that underwent Angptl2-deficient bone marrow transplantation. Expression levels of proinflammatory cytokines and metalloproteinase-9 in Angptl2-deficient macrophages were significantly decreased, and those decreases were rescued by treatment of Angptl2 deficient macrophages with exogenous Angptl2. Macrophage-derived Angptl2 contributes to AAA development by inducing inflammation and degradation of extracellular matrix in the vessel wall, suggesting that targeting the Angptl2-induced inflammatory axis in macrophages could represent a new strategy for AAA therapy.

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Angiopoietin-Like Protein 2 and Risk of Type 2 Diabetes in a General Japanese Population

Yasufumi Doi, Toshiharu Ninomiya, Yoichiro Hirakawa … (2012)

OBJECTIVE To examine, for the first time, the association between a novel inflammatory cytokine, angiopoietin-like protein (ANGPTL) 2, and the development of type 2 diabetes (T2DM). RESEARCH DESIGN AND METHODS A total of 2,164 community-dwelling Japanese individuals aged 40 to 79 years without diabetes were followed up for 7 years. Serum ANGPTL2 levels were divided into quartile categories at baseline: <2.15, 2.16–2.71, 2.72–3.40, and ≥3.41 ng/mL. During follow-up, 221 participants developed T2DM. RESULTS In multivariate analyses, after adjusting for comprehensive risk factors and high-sensitivity C-reactive protein (hs-CRP) levels, the risk of developing T2DM was significantly higher in the highest ANGPTL2 quartile than in the lowest quartile (hazard ratio, 1.80; 95% CI, 1.14–2.85; P = 0.01). CONCLUSIONS Elevated serum ANGPTL2 levels were positively associated with the development of T2DM in a general population, independent of other risk factors including hs-CRP levels.

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Author and article information

Journal

Journal ID (nlm-ta): World J Gastroenterol

Journal ID (iso-abbrev): World J. Gastroenterol

Journal ID (publisher-id): WJG

Title: World Journal of Gastroenterology

Publisher: Baishideng Publishing Group Inc

ISSN (Print): 1007-9327

ISSN (Electronic): 2219-2840

Publication date (Print): 21 December 2016

Publication date (Electronic): 21 December 2016

Volume: 22

Issue: 47

Pages: 10364-10370

Affiliations

Wei-Zhong Sheng, Yu-Sheng Chen, Bo Zhang, Wei-Dong Gao, Department of General Surgery, Fudan University Affiliated Zhongshan Hospital, Shanghai 200032, China

Chuan-Tao Tu, Juan He, Department of Digestion, Fudan University Affiliated Zhongshan Hospital, Shanghai 200032, China

Author notes

Author contributions: Sheng WZ, Chen YS contributed equally to this work; Sheng WZ, Chen YS and Gao WD designed the research; Sheng WZ, Chen YS, Tu CT, He J, Zhang B and Gao WD performed the research; Chen YS, Tu CT, He J and Zhang B contributed new reagents/analytic tools; Sheng WZ and Chen YS analyzed the data; Sheng WZ and Gao WD wrote the paper.

Correspondence to: Wei-Dong Gao, MD, Associate Professor, Department of General Surgery, Fudan University Affiliated Zhongshan Hospital, No. 180 Fenglin Road, Shanghai 200032, China. gao.weidong@ 123456zs-hospital.sh.cn

Telephone: +86-21-64041990 Fax: +86-21-64041990

Article

Other ID: jWJG.v22.i47.pg10364

DOI: 10.3748/wjg.v22.i47.10364

PMC ID: 5175248

SO-VID: 88895dbd-1f81-475f-ac5c-ed3cd381ba0f

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This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial.

ANGPTL2 expression in gastric cancer tissues and cells and its biological behavior

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Abstract

AIM

METHODS

RESULTS

CONCLUSION

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Karger: Oncology

Most cited references 37

Gastric cancer and the epoch of immunotherapy approaches.

Macrophage-derived angiopoietin-like protein 2 accelerates development of abdominal aortic aneurysm.

Angiopoietin-Like Protein 2 and Risk of Type 2 Diabetes in a General Japanese Population

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