Advertisement
Original Article| Volume 166, ISSUE 6, P602-613, December 2015

Upregulation of a disintegrin and metalloprotease 8 is associated with progression and prognosis of patients with gastric cancer

  • Jintuan Huang
    Affiliations
    Department of Gastrointestinal Surgery, The Sixth Affiliated Hospital of Sun Yat-Sen University (Guangdong Gastrointestinal and Anal Hospital), Sun Yat-Sen University, Guangzhou, PR China

    Guangdong Institute of Gastroenterology, Guangzhou, PR China
    Search for articles by this author
  • Yang Bai
    Affiliations
    Department of Gastrointestinal Surgery, The Sixth Affiliated Hospital of Sun Yat-Sen University (Guangdong Gastrointestinal and Anal Hospital), Sun Yat-Sen University, Guangzhou, PR China

    Guangdong Institute of Gastroenterology, Guangzhou, PR China

    Department of Colorectal Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, PR China
    Search for articles by this author
  • Lijun Huo
    Affiliations
    Department of Ophthalmology, The First Affiliated Hospital of Sun Yat-Sen University, Sun Yat-Sen University, Guangzhou, PR China
    Search for articles by this author
  • Jian Xiao
    Affiliations
    Department of Medical Oncology, The Sixth Affiliated Hospital of Sun Yat-Sen University (Guangdong Gastrointestinal and Anal Hospital), Sun Yat-Sen University, Guangzhou, PR China
    Search for articles by this author
  • Xinjuan Fan
    Affiliations
    Guangdong Institute of Gastroenterology, Guangzhou, PR China
    Search for articles by this author
  • Zihuan Yang
    Affiliations
    Guangdong Institute of Gastroenterology, Guangzhou, PR China
    Search for articles by this author
  • Hao Chen
    Affiliations
    Department of Gastrointestinal Surgery, The Sixth Affiliated Hospital of Sun Yat-Sen University (Guangdong Gastrointestinal and Anal Hospital), Sun Yat-Sen University, Guangzhou, PR China
    Search for articles by this author
  • Zuli Yang
    Correspondence
    Reprint requests: Zuli Yang, Department of Gastrointestinal Surgery, The Sixth Affiliated Hospital of Sun Yat-Sen University (Guangdong Gastrointestinal and Anal Hospital); Guangdong Institute of Gastroenterology, 26 Yuancun Erheng Road, Guangzhou 510655, PR China
    Affiliations
    Department of Gastrointestinal Surgery, The Sixth Affiliated Hospital of Sun Yat-Sen University (Guangdong Gastrointestinal and Anal Hospital), Sun Yat-Sen University, Guangzhou, PR China

    Guangdong Institute of Gastroenterology, Guangzhou, PR China
    Search for articles by this author
      A disintegrin and metalloprotease 8 (ADAM8) is involved in the tumorigenesis of several types of solid tumors. However, its exact role in gastric cancer (GC) remains unclear. The aim of this study was to evaluate the clinical significance of ADAM8 in GC and to explore its biological effects on gastric carcinogenesis. In this study, quantitative reverse transcription–polymerase chain reaction, Western blotting, and immunohistochemical staining analysis revealed that ADAM8 messenger RNA expression was significantly upregulated in GC tissues compared with noncancerous tissues (P = 0.004), and that positive ADAM8 expression is much more common in tumor tissues compared with normal tissues (P < 0.001) and is correlated with T stage (P = 0.036), N stage (P = 0.048), vessel invasion (P = 0.002), and a shorter patient overall survival (P = 0.024). In vitro assay indicated that ADAM8 overexpression promoted cell growth and increased migration and invasion abilities by decreasing the p-p38/p-extracellular regulated protein kinases (p-ERK) ratio. In conclusion, ADAM8 promotes GC cell proliferation and invasion, and its expression is positively correlated with poor survival, indicating that it might be a promising target in GC therapy.

      Abbreviations:

      ADAM8 (a disintegrin and metalloprotease 8), GC (gastric cancer), OS (overall survival)
      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to Translational Research
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • World Health Organization (WHO)
        Cancer fact sheet.
        World Health Organization, 2011 (Available at:) (Accessed September 26, 2011)
        • Yang L.
        Incidence and mortality of gastric cancer in China.
        World J Gastroenterol. 2006; 12: 17-20
        • Zhao Z.S.
        • Wang Y.Y.
        • Chu Y.Q.
        • et al.
        SPARC is associated with gastric cancer progression and poor survival of patients.
        Clin Cancer Res. 2010; 16: 260-268
        • Cidon E.U.
        • Cuenca I.J.
        Gastric adenocarcinoma: is computed tomography (CT) useful in preoperative staging?.
        Clin Med Oncol. 2009; 3: 91-97
        • Seevaratnam R.
        • Cardoso R.
        • McGregor C.
        • et al.
        How useful is preoperative imaging for tumor, node, metastasis (TNM) staging of gastric cancer? A meta-analysis.
        Gastric Cancer. 2012; 15: S3-S18
        • Funasaka T.
        • Raz A.
        The role of autocrine motility factor in tumor and tumor microenvironment.
        Cancer Metastasis Rev. 2007; 26: 725-735
        • Ellerman J.E.
        • Brown C.K.
        • de Vera M.
        • et al.
        Masquerader: high mobility group box-1 and cancer.
        Clin Cancer Res. 2007; 13: 2836-2848
        • Scartozzi M.
        • Bittoni A.
        • Pistelli M.
        • et al.
        Toward molecularly selected chemotherapy for advanced gastric cancer: state of the art and future perspectives.
        Cancer Treat Rev. 2009; 35: 451-462
        • Panani A.D.
        Cytogenetic and molecular aspects of gastric cancer: clinical implications.
        Cancer Lett. 2008; 266: 99-115
        • Wang Y.Y.
        • Ye Z.Y.
        • Li L.
        • et al.
        ADAM10 is associated with gastric cancer progression and prognosis of patients.
        J Surg Oncol. 2011; 103: 116-123
        • Xu P.
        • Derynck R.
        Direct activation of TACE-mediate dectodo-mainshedding by p38MAP kinaser egulates EGF receptor-dependent cell proliferation.
        Mol Cell. 2010; 37: 551-566
        • Li W.
        • Ye F.
        • Wang D.
        • et al.
        Protein predictive signatures for lymph node metastasis of gastric cancer.
        Int J Cancer. 2013; 132: 1851-1859
        • Fourie A.M.
        • Coles F.
        • Moreno V.
        • et al.
        Catalytic activity of ADAM8, ADAM15, and MDC-L (ADAM28) on synthetic peptide substrates and in ectodomain cleavage of CD23.
        J Biol Chem. 2003; 278: 30469-30477
        • Romagnoli M.
        • Mineva N.D.
        • Polmear M.
        • et al.
        ADAM8 expression in invasive breast cancer promotes tumor dissemination and metastasis.
        EMBO Mol Med. 2014; 6: 278-294
        • Zhang R.
        • Yuan Y.
        • Zuo J.
        • et al.
        Prognostic and clinical implication of a disintegrin and metalloprotease 8 expression in pediatric medulloblastoma.
        J Neurol Sci. 2012; 323: 46-51
        • Gillett C.E.
        • Springall R.J.
        • Barnes D.M.
        • et al.
        Multiple tissue core arrays in histopathology research: a validation study.
        J Pathol. 2000; 192: 549-553
        • Fan X.J.
        • Wan X.B.
        • Yang Z.L.
        • et al.
        Snail promotes lymph node metastasis and twist enhances tumor deposit formation through epithelial-mesenchymal transition in colorectal cancer.
        Hum Pathol. 2013; 44: 173-180
        • Arribas J.
        • Bech-Serra J.J.
        • Santiago-Josefat B.
        • et al.
        ADAMs, cell migration and cancer.
        Cancer Metastasis Rev. 2006; 25: 57-68
        • Handsley M.M.
        • Edwards D.R.
        Metalloproteinases and their inhibitors in tumor angiogenesis.
        Int J Cancer. 2005; 115: 849-860
        • Ebi M.
        • Kataoka H.
        • Shimura T.
        • et al.
        TGFβ induces proHB-EGF shedding and EGFR transactivation through ADAM activation in gastric cancer cells.
        Biochem Biophys Res Commun. 2010; 402: 449-454
        • Carl-McGrath S.
        • Lendeckel U.
        • Ebert M.
        • et al.
        The disintegrin-metalloproteinases ADAM9, ADAM12, and ADAM15 are upregulated in gastric cancer.
        Int J Oncol. 2005; 26: 17-24
        • Ray A.
        • Dhar S.
        • Ray B.K.
        Transforming growth factor-beta1-mediated activation of NF-kappaB contributes to enhanced ADAM-12 expression in mammary carcinoma cells.
        Mol Cancer Res. 2010; 8: 1261-1270
        • Yoshimura T.
        • Tomita T.
        • Dixon M.
        • et al.
        ADAMs (a disintegrin and metalloproteinase) messenger RNA expression in helicobacter pylori—infected, normal, and neoplastic gastric mucosa.
        J Infect Dis. 2002; 185: 332-340
        • Kim K.E.
        • Song H.
        • Hahm C.
        • et al.
        Expression of ADAM33 is a novel regulatory mechanism in IL-18-secreted process in gastric cancer.
        J Immunol. 2009; 182: 3548-3555
        • Baren J.P.
        • Stewart G.D.
        • Stokes A.
        • et al.
        mRNA profiling of the cancer degradome in oesophago-gastric adenocarcinoma.
        Br J Cancer. 2012; 107: 143-149
        • Fritzsche F.R.
        • Jung M.
        • Xu C.
        • et al.
        ADAM8 expression in prostate cancer is associated with parameters of unfavorable prognosis.
        Virchows Arch. 2006; 449: 628-636
        • Ishikawa N.
        • Daigo Y.
        • Yasui W.
        • et al.
        ADAM8 as a novel serological and histochemical marker for lung cancer.
        Clin Cancer Res. 2004; 10: 8363-8370
        • Roemer A.
        • Schwettmann L.
        • Jung M.
        • et al.
        The membrane proteases Adams and hepsin are differentially expressed in renal cell carcinoma. Are they potential tumor markers?.
        J Urol. 2004; 172: 2162-2166
        • Wildeboer D.
        • Naus S.
        • Amy Sang Q.X.
        • et al.
        Metalloproteinase disintegrins ADAM8 and ADAM19 are highly regulated in human primary brain tumors and their expression levels and activities are associated with invasiveness.
        J Neuropathol Exp Neurol. 2006; 65: 516-527
        • Aguirre-Ghiso J.A.
        • Estrada Y.
        • Liu D.
        • et al.
        ERK (MAPK) activity as a determinant of tumor growth and dormancy; regulation by p38 (SAPK).
        Cancer Res. 2003; 63: 1684-1695