Skip to main content

Advertisement

Log in

ADAM-17 over-expression in gallbladder carcinoma correlates with poor prognosis of patients

  • Original Paper
  • Published:
Medical Oncology Aims and scope Submit manuscript

Abstract

The ADAMs is a multi-functional gene family of membrane proteins possessing a disintegrin and metalloprotease domain. They have potential implications for the metastasis of human tumor cells via cell adhesion and protease activities. However, no studies have yet comprehensively examined the expression of ADAMs in gallbladder carcinoma. The aim of this study was to test the hypothesis that ADAM-17 (otherwise known as tumor necrosis factor-α converting enzyme) is involved in the progression of gallbladder carcinoma. Two hundreds samples of gallbladder carcinoma and sixty non-cancerous gallbladder samples were used to measure the expression of total ADAM-17 by enzyme-linked immunosorbent assay, and the precursor and active forms by western blotting analysis. Expression of ADAM-17 was significantly increased in tumors with high histological grade and pT stage compared with low histological grade and pT stage tumors and was not associated with patients’ gender, age, histological type, and resection margin involvement. Patients with high expression of ADAM-17 had a significantly shorter overall survival compared with those with low expression. Significantly, the prognostic impact of ADAM-17 was independent of conventional prognostic factors for gallbladder carcinoma. The current study demonstrated that the over-expression of ADAM-17 in patients with gallbladder carcinoma was linked closely with histological grade, pT stage and prognosis, and thus provides further impetus for exploiting ADAM-17 as new target for the treatment of gallbladder carcinoma.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1

Similar content being viewed by others

References

  1. Roa I, De Aretxabala X, Araya JC, Roa J. Preneoplastic lesions in gallbladder cancer. J Surg Oncol. 2006;93:615–23.

    Article  PubMed  Google Scholar 

  2. Lewis JT, Talwalkar JA, Rosen CB, Smyrk TC, Abraham SC. Prevalence and risk factors for gallbladder neoplasia in patients with primary sclerosing cholangitis: evidence for a metaplasia-dysplasiacarcinoma sequence. Am J Surg Pathol. 2007;31:907–13.

    Article  PubMed  Google Scholar 

  3. Misra S, Chaturvedi A, Misra NC, Sharma ID. Carcinoma of the gallbladder. Lancet Oncol. 2003;4:167–76.

    Article  PubMed  Google Scholar 

  4. Edwards DR, Handsley MM, Pennington CJ. The ADAM metalloproteinases. Mol Aspects Med. 2008;29:258–89.

    Article  PubMed  CAS  Google Scholar 

  5. Porter S, Clark IM, Kevorkian L, Edwards DR. The ADAMTS metalloproteinases. Biochem J. 2005;386:15–27.

    Article  PubMed  CAS  Google Scholar 

  6. Borrell-Pages M, Rojo F, Albanell J, Baselga J, Arribas J. TACE is required for the activation of the EGFR by TGF-alpha in tumors. EMBO J. 2003;22:1114–24.

    Article  PubMed  CAS  Google Scholar 

  7. Brou C, Logeat F, Gupta N, et al. A novel proteolytic cleavage involved in notch signaling: the role of the disintegrin-metalloprotease TACE. Mol Cell. 2000;5:207–16.

    Article  PubMed  CAS  Google Scholar 

  8. Horiuchi K, Zhou HM, Kelly K, Manova K, Blobel CP. Evaluation of the contributions of ADAMs 9, 12, 15, 17, and 19 to heart development and ectodomain shedding of neuregulins beta1 and beta2. Dev Biol. 2005;283:459–71.

    Article  PubMed  CAS  Google Scholar 

  9. McGowan PM, Ryan BM, Hill AD, Dermott E, Higgins NO, Duffy MJ. ADAM-17 expression in breast cancer correlates with variables of tumor progression. Clin Cancer Res. 2007;13:2335–43.

    Article  PubMed  CAS  Google Scholar 

  10. Takamune Y, Ikebe T, Nagano O, et al. ADAM-17 associated with CD44 cleavage and metastasis in oral squamous cell carcinoma. Virchows Arch. 2007;450:169–77.

    Article  PubMed  CAS  Google Scholar 

  11. Fan YZ, Zhang JT, Yang HC, Yang YQ. Expression of MMP-2, TIMP-2 protein and the ratio of MMP-2/TIMP-2 in gallbladder carcinoma and their significance. World J Gastroenterol. 2002;8:1138–43.

    PubMed  CAS  Google Scholar 

  12. Ma HB, Hu HT, Di ZL, et al. Association of cyclin D1, p16 and retinoblastoma protein expressions with prognosis and metastasis of gallbladder carcinoma. World J Gastroenterol. 2005;11:744–7.

    PubMed  Google Scholar 

  13. Moss ML, Jin SL, Milla ME, et al. Cloning of a disintegrin metalloproteinase that processes precursor tumour-necrosis factor-alpha. Nature. 1997;385:733–6.

    Article  PubMed  CAS  Google Scholar 

  14. Huovila AP, Turner AJ, Pelto-Huikko M, Karkkainen I, Ortiz RM. Shedding light on ADAM metalloproteinases. Trends Biochem Sci. 2005;30:413–22.

    Article  PubMed  CAS  Google Scholar 

  15. Zhao J, Chen H, Peschon JJ, et al. Pulmonary hypoplasia in mice lacking tumor necrosis factor-alpha converting enzyme indicates an indispensable role for cell surface protein shedding during embryonic lung branching morphogenesis. Dev Biol. 2001;232:204–18.

    Article  PubMed  CAS  Google Scholar 

  16. Shi W, Chen H, Sun J, et al. TACE is required for fetal murine cardiac development and modeling. Dev Biol. 2003;261:371–80.

    Article  PubMed  CAS  Google Scholar 

  17. Gooz M. ADAM-17: the enzyme that does it all. Crit Rev Biochem Mol Biol. 2010, in press.

  18. Blanchot-Jossic F, Jarry A, Masson D, et al. Up-regulated expression of ADAM-17 in human colon carcinoma: co-expression with EGFR in neoplastic and endothelial cells. J Pathol. 2005;207:156–63.

    Article  PubMed  CAS  Google Scholar 

  19. Tanaka Y, Miyamoto S, Suzuki SO, et al. Clinical significance of heparin-binding epidermal growth factor-like growth factor and a disintegrin and metalloprotease 17 expression in human ovarian cancer. Clin Cancer Res. 2005;11:4783–92.

    Article  PubMed  CAS  Google Scholar 

  20. Fabre-Lafay S, Garrido-Urbani S, Reymond N, Goncalves A, Dubreuil P, Lopez M. Nectin-4, a new serological breast cancer marker, is a substrate for tumor necrosis factor-a-converting enzyme (TACE)/ADAM-17. J Biol Chem. 2005;280:19543–50.

    Article  PubMed  CAS  Google Scholar 

  21. Karan D, Lin FC, Bryan M, et al. Expression of ADAMs (a disintegrin and metalloproteases) and TIMP-3 (tissue inhibitor of metalloproteinase-3) in human prostatic adenocarcinoma. Int J Oncol. 2003;23:1365–71.

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Zhansheng Deng.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Wu, K., Liao, M., Liu, B. et al. ADAM-17 over-expression in gallbladder carcinoma correlates with poor prognosis of patients. Med Oncol 28, 475–480 (2011). https://doi.org/10.1007/s12032-010-9481-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12032-010-9481-8

Keywords

Navigation