Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Oncology Letters
      • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Biomedical Reports
      • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • Information for Authors
    • Information for Reviewers
    • Information for Librarians
    • Information for Advertisers
    • Conferences
  • Language Editing
Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • For Authors
    • For Reviewers
    • For Librarians
    • For Advertisers
    • Conferences
  • Language Editing
Login Register Submit
  • This site uses cookies
  • You can change your cookie settings at any time by following the instructions in our Cookie Policy. To find out more, you may read our Privacy Policy.

    I agree
Search articles by DOI, keyword, author or affiliation
Search
Advanced Search
presentation
Molecular Medicine Reports
Join Editorial Board Propose a Special Issue
Print ISSN: 1791-2997 Online ISSN: 1791-3004
Journal Cover
August-2015 Volume 12 Issue 2

Full Size Image

Sign up for eToc alerts
Recommend to Library

Journals

International Journal of Molecular Medicine

International Journal of Molecular Medicine

International Journal of Molecular Medicine is an international journal devoted to molecular mechanisms of human disease.

International Journal of Oncology

International Journal of Oncology

International Journal of Oncology is an international journal devoted to oncology research and cancer treatment.

Molecular Medicine Reports

Molecular Medicine Reports

Covers molecular medicine topics such as pharmacology, pathology, genetics, neuroscience, infectious diseases, molecular cardiology, and molecular surgery.

Oncology Reports

Oncology Reports

Oncology Reports is an international journal devoted to fundamental and applied research in Oncology.

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine is an international journal devoted to laboratory and clinical medicine.

Oncology Letters

Oncology Letters

Oncology Letters is an international journal devoted to Experimental and Clinical Oncology.

Biomedical Reports

Biomedical Reports

Explores a wide range of biological and medical fields, including pharmacology, genetics, microbiology, neuroscience, and molecular cardiology.

Molecular and Clinical Oncology

Molecular and Clinical Oncology

International journal addressing all aspects of oncology research, from tumorigenesis and oncogenes to chemotherapy and metastasis.

World Academy of Sciences Journal

World Academy of Sciences Journal

Multidisciplinary open-access journal spanning biochemistry, genetics, neuroscience, environmental health, and synthetic biology.

International Journal of Functional Nutrition

International Journal of Functional Nutrition

Open-access journal combining biochemistry, pharmacology, immunology, and genetics to advance health through functional nutrition.

International Journal of Epigenetics

International Journal of Epigenetics

Publishes open-access research on using epigenetics to advance understanding and treatment of human disease.

Medicine International

Medicine International

An International Open Access Journal Devoted to General Medicine.

Journal Cover
August-2015 Volume 12 Issue 2

Full Size Image

Sign up for eToc alerts
Recommend to Library

  • Article
  • Citations
    • Cite This Article
    • Download Citation
    • Create Citation Alert
    • Remove Citation Alert
    • Cited By
  • Similar Articles
    • Related Articles (in Spandidos Publications)
    • Similar Articles (Google Scholar)
    • Similar Articles (PubMed)
  • Download PDF
  • Download XML
  • View XML
Article Open Access

Downregulation of A disintegrin and metallopeptidase with thrombospondin motif type 1 by DNA hypermethylation in human gastric cancer

  • Authors:
    • Jing Chen
    • Chundong Zhang
    • Xiaoyang Xu
    • Xinjiang Zhu
    • Dongqiu Dai
  • View Affiliations / Copyright

    Affiliations: Department of Gastrointestinal Surgery, The Fourth Affiliated Hospital of China Medical University, Shenyang, Liaoning 110032, P.R. China
    Copyright: © Chen et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY_NC 3.0].
  • Pages: 2487-2494
    |
    Published online on: April 23, 2015
       https://doi.org/10.3892/mmr.2015.3667
  • Expand metrics +
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )
Cited By (CrossRef): 0 citations Loading Articles...

This article is mentioned in:



Abstract

A disintegrin and metallopeptidase with thrombospondin motif type 1 (ADAMTS1) is a metalloproteinase with antiangiogenic activity. It was previously observed that the mRNA and protein levels of ADAMTS1 are downregulated in primary gastric tumors. The aim of the present study was to examine whether the reduction in the expression of ADAMTS1 is due to aberrant methylation of the gene in primary gastric tumor tissues and gastric cancer cell lines. In addition, the association between ADAMTS1 methylation and clinicopathological features in were investigated in patients with primary gastric cancer. The results revealed that the frequency of ADAMTS1 methylation in primary gastric tumor tissues was significantly higher, compared with the corresponding normal gastric tissues. The relative mRNA expression levels of ADAMTS1 were significantly lower in the methylated primary gastric tumor tissues, compared with the unmethylated primary gastric tumor tissuess. A significant association was observed between the ADAMTS1 methylation status and the depth of tumor invasion and tumor, node, metastasis stage in primary gastric cancer. The mRNA expression of ADAMTS1 was significantly lower in 60% (3 of 5) of the gastric cancer cell lines. The relative mRNA expression levels of ADAMTS1 were significantly lower in the methylated gastric cancer cell lines, compared with the unmethylated gastric cancer cell lines. Furthermore, the expression of ADAMTS1 was significantly restored following treatment with the 5‑Aza‑2'‑deoxycytidine demethylating agent in the MGC‑803, HGC‑27 and AGS gastric cancer cell lines, and the demethylation of the MGC‑803 cell line inhibited cell invasion. Together, these results suggested for the first time, to the best of our knowledge, ADAMTS1 as a novel antitumor protease, and this function was lost following epigenetic silencing in the gastric cancer cells and gastric tumor tissues. Therefore, the aberrant methylation of ADAMTS1 may be involved in the development and progression of gastric cancer.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

View References

1 

Porter S, Clark IM, Kevorkian L and Edwards DR: The ADAMTS metalloproteinases. Biochem J. 386:15–27. 2005. View Article : Google Scholar :

2 

Tang BL and Hong W: ADAMTS: a novel family of proteases with an ADAM protease domain and thrombospondin 1 repeats. FEBS Lett. 445:223–225. 1999. View Article : Google Scholar : PubMed/NCBI

3 

Kaushal GP and Shah SV: The new kids on the block: ADAMTSs, potentially multifunctional metalloproteinases of the ADAM family. J Clin Invest. 105:1335–1337. 2000. View Article : Google Scholar : PubMed/NCBI

4 

Colige A, Sieron AL, Li SW, et al: Human Ehlers-Danlos syndrome type VII C and bovine dermatosparaxis are caused by mutations in the procollagen I N-proteinase gene. Am J Hum Genet. 65:308–317. 1999. View Article : Google Scholar : PubMed/NCBI

5 

Levy GG, Nichols WC, Lian EC, et al: Mutations in a member of the ADAMTS gene family cause thrombotic thrombocytopenic purpura. Nature. 413:488–494. 2001. View Article : Google Scholar : PubMed/NCBI

6 

Dunn JR, Panutsopulos D, Shaw MW, et al: METH-2 silencing and promoter hypermethylation in NSCLC. Br J Cancer. 91:1149–1154. 2004.PubMed/NCBI

7 

Glasson SS, Askew R, Sheppard B, et al: Characterization of and osteoarthritis susceptibility in ADAMTS-4-knockout mice. Arthritis Rheum. 50:2547–2558. 2004. View Article : Google Scholar : PubMed/NCBI

8 

Porter S, Scott SD, Sassoon EM, et al: Dysregulated expression of adamalysin-thrombospondin genes in human breast carcinoma. Clin Cancer Res. 10:2429–2440. 2004. View Article : Google Scholar : PubMed/NCBI

9 

Llamazares M, Obaya AJ, Moncada-Pazos A, et al: The ADAMTS12 metalloproteinase exhibits anti-tumorigenic properties through modulation of the Ras-dependent ERK signalling pathway. J Cell Sci. 120:3544–3552. 2007. View Article : Google Scholar : PubMed/NCBI

10 

Keightley MC, Sales KJ and Jabbour HN: PGF2alpha-F-prostanoid receptor signalling via ADAMTS1 modulates epithelial cell invasion and endothelial cell function in endometrial cancer. BMC Cancer. 10:4882010. View Article : Google Scholar

11 

Mochizuki S and Okada Y: ADAMs in cancer cell proliferation and progression. Cancer Sci. 98:621–628. 2007. View Article : Google Scholar : PubMed/NCBI

12 

Jones GC and Riley GP: ADAMTS proteinases: a multi-domain, multi-functional family with roles in extracellular matrix turnover and arthritis. Arthritis Res Ther. 7:160–169. 2005. View Article : Google Scholar : PubMed/NCBI

13 

Sandy JD, Westling J, Kenagy RD, et al: Versican V1 proteolysis in human aorta in vivo occurs at the Glu441-Ala442 bond, a site that is cleaved by recombinant ADAMTS-1 and ADAMTS-4. J Biol Chem. 276:13372–13378. 2001. View Article : Google Scholar : PubMed/NCBI

14 

Russell DL, Doyle KM, Ochsner SA, Sandy JD and Richards JS: Processing and localization of ADAMTS-1 and proteolytic cleavage of versican during cumulus matrix expansion and ovulation. J Biol Chem. 278:42330–42339. 2003. View Article : Google Scholar : PubMed/NCBI

15 

Kuno K, Bannai K, Hakozaki M, Matsushima K and Hirose K: The carboxyl-terminal half region of ADAMTS-1 suppresses both tumorigenicity and experimental tumor metastatic potential. Biochem Biophys Res Commun. 319:1327–1333. 2004. View Article : Google Scholar : PubMed/NCBI

16 

Obika M, Ogawa H, Takahashi K, et al: Tumor growth inhibitory effect of ADAMTS1 is accompanied by the inhibition of tumor angiogenesis. Cancer Sci. 103:1889–1897. 2012. View Article : Google Scholar : PubMed/NCBI

17 

Luque A, Carpizo DR and Iruela-Arispe ML: ADAMTS1/METH1 inhibits endothelial cell proliferation by direct binding and sequestration of VEGF165. J Biol Chem. 278:23656–23665. 2003. View Article : Google Scholar : PubMed/NCBI

18 

Gustavsson H, Wang W, Jennbacken K, Welen K and Damber JE: ADAMTS1, a putative anti-angiogenic factor, is decreased in human prostate cancer. BJU Int. 104:1786–1790. 2009. View Article : Google Scholar : PubMed/NCBI

19 

Freitas VM, do AJB, Silva TA, et al: Decreased expression of ADAMTS-1 in human breast tumors stimulates migration and invasion. Mol Cancer. 12:22013. View Article : Google Scholar : PubMed/NCBI

20 

Martino-Echarri E, Fernandez-Rodriguez R, Rodriguez-Baena FJ, et al: Contribution of ADAMTS1 as a tumor suppressor gene in human breast carcinoma. Linking its tumor inhibitory properties to its proteolytic activity on nidogen-1 and nidogen-2. Int J Cancer. 133:2315–2324. 2013. View Article : Google Scholar : PubMed/NCBI

21 

Toyota M, Ahuja N, Suzuki H, et al: Aberrant methylation in gastric cancer associated with the CpG island methylator phenotype. Cancer Res. 59:5438–5442. 1999.PubMed/NCBI

22 

Chen J, Zhi Y, Chang X, Zhang S and Dai D: Expression of ADAMTS1 and its correlation with angiogenesis in primary gastric cancer and lymph node metastasis. Dig Dis Sci. 58:405–413. 2013. View Article : Google Scholar

23 

Zhi Y, Chen J, Zhang S, Chang X, Ma J and Dai D: Downregulation of CXCL12 by DNA hypermethylation and its involvement in gastric cancer metastatic progression. Dig Dis Sci. 57:650–659. 2012. View Article : Google Scholar

24 

Herman JG, Graff JR, Myohanen S, Nelkin BD and Baylin SB: Methylation-specific PCR: a novel PCR assay for methylation status of CpG islands. Proc Natl Acad Sci USA. 93:9821–9826. 1996. View Article : Google Scholar : PubMed/NCBI

25 

Choi JE, Kim DS, Kim EJ, et al: Aberrant methylation of ADAMTS1 in non-small cell lung cancer. Cancer Genet Cytogenet. 187:80–84. 2008. View Article : Google Scholar : PubMed/NCBI

26 

Lee NV, Sato M, Annis DS, et al: ADAMTS1 mediates the release of antiangiogenic polypeptides from TSP1 and 2. EMBO J. 25:5270–5283. 2006. View Article : Google Scholar : PubMed/NCBI

27 

Masui T, Hosotani R, Tsuji S, et al: Expression of METH-1 and METH-2 in pancreatic cancer. Clin Cancer Res. 7:3437–3443. 2001.PubMed/NCBI

28 

Ahlquist T, Lind GE, Costa VL, et al: Gene methylation profiles of normal mucosa and benign and malignant colorectal tumors identify early onset markers. Mol Cancer. 7:942008. View Article : Google Scholar

29 

Liu YJ, Xu Y and Yu Q: Full-length ADAMTS-1 and the ADAMTS-1 fragments display pro- and antimetastatic activity, respectively. Oncogene. 25:2452–2467. 2006. View Article : Google Scholar

30 

Tyan SW, Hsu CH, Peng KL, et al: Breast cancer cells induce stromal fibroblasts to secrete ADAMTS1 for cancer invasion through an epigenetic change. PLoS One. 7:e351282012. View Article : Google Scholar : PubMed/NCBI

31 

Ricciardelli C, Frewin KM, Tan IA, et al: The ADAMTS1 protease gene is required for mammary tumor growth and metastasis. Am J Pathol. 179:3075–3085. 2011. View Article : Google Scholar : PubMed/NCBI

32 

Kohno T, Otsuka A, Girard L, et al: A catalog of genes homozygously deleted in human lung cancer and the candidacy of PTPRD as a tumor suppressor gene. Genes Chromosomes Cancer. 49:342–352. 2010.PubMed/NCBI

33 

Yegnasubramanian S, Wu Z, Haffner MC, et al: Chromosome-wide mapping of DNA methylation patterns in normal and malignant prostate cells reveals pervasive methylation of gene-associated and conserved intergenic sequences. BMC Genomics. 12:3132011. View Article : Google Scholar : PubMed/NCBI

34 

Lind GE, Kleivi K, Meling GI, et al: ADAMTS1, CRABP1 and NR3C1 identified as epigenetically deregulated genes in colorectal tumorigenesis. Cell Oncol. 28:259–272. 2006.

35 

Li Z, Zhang W, Shao Y, et al: High-resolution melting analysis of ADAMTS18 methylation levels in gastric, colorectal and pancreatic cancers. Med Oncol. 27:998–1004. 2010. View Article : Google Scholar

36 

Zhang C, Shao Y, Zhang W, et al: High-resolution melting analysis of ADAMTS9 methylation levels in gastric, colorectal and pancreatic cancers. Cancer Genet Cytogenet. 196:38–44. 2010. View Article : Google Scholar

37 

Singh KP, Treas J, Tyagi T and Gao W: DNA demethylation by 5-aza-2-deoxycytidine treatment abrogates 17 beta-estradiol-induced cell growth and restores expression of DNA repair genes in human breast cancer cells. Cancer Lett. 316:62–69. 2012. View Article : Google Scholar

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Chen J, Zhang C, Xu X, Zhu X and Dai D: Downregulation of A disintegrin and metallopeptidase with thrombospondin motif type 1 by DNA hypermethylation in human gastric cancer. Mol Med Rep 12: 2487-2494, 2015.
APA
Chen, J., Zhang, C., Xu, X., Zhu, X., & Dai, D. (2015). Downregulation of A disintegrin and metallopeptidase with thrombospondin motif type 1 by DNA hypermethylation in human gastric cancer. Molecular Medicine Reports, 12, 2487-2494. https://doi.org/10.3892/mmr.2015.3667
MLA
Chen, J., Zhang, C., Xu, X., Zhu, X., Dai, D."Downregulation of A disintegrin and metallopeptidase with thrombospondin motif type 1 by DNA hypermethylation in human gastric cancer". Molecular Medicine Reports 12.2 (2015): 2487-2494.
Chicago
Chen, J., Zhang, C., Xu, X., Zhu, X., Dai, D."Downregulation of A disintegrin and metallopeptidase with thrombospondin motif type 1 by DNA hypermethylation in human gastric cancer". Molecular Medicine Reports 12, no. 2 (2015): 2487-2494. https://doi.org/10.3892/mmr.2015.3667
Copy and paste a formatted citation
x
Spandidos Publications style
Chen J, Zhang C, Xu X, Zhu X and Dai D: Downregulation of A disintegrin and metallopeptidase with thrombospondin motif type 1 by DNA hypermethylation in human gastric cancer. Mol Med Rep 12: 2487-2494, 2015.
APA
Chen, J., Zhang, C., Xu, X., Zhu, X., & Dai, D. (2015). Downregulation of A disintegrin and metallopeptidase with thrombospondin motif type 1 by DNA hypermethylation in human gastric cancer. Molecular Medicine Reports, 12, 2487-2494. https://doi.org/10.3892/mmr.2015.3667
MLA
Chen, J., Zhang, C., Xu, X., Zhu, X., Dai, D."Downregulation of A disintegrin and metallopeptidase with thrombospondin motif type 1 by DNA hypermethylation in human gastric cancer". Molecular Medicine Reports 12.2 (2015): 2487-2494.
Chicago
Chen, J., Zhang, C., Xu, X., Zhu, X., Dai, D."Downregulation of A disintegrin and metallopeptidase with thrombospondin motif type 1 by DNA hypermethylation in human gastric cancer". Molecular Medicine Reports 12, no. 2 (2015): 2487-2494. https://doi.org/10.3892/mmr.2015.3667
Follow us
  • Twitter
  • LinkedIn
  • Facebook
About
  • Spandidos Publications
  • Careers
  • Cookie Policy
  • Privacy Policy
How can we help?
  • Help
  • Live Chat
  • Contact
  • Email to our Support Team