Urologic Oncology: Seminars and Original Investigations
Volume 24, Issue 2 , Pages 97-108, March 2006

Overexpression of α-defensin is associated with bladder cancer invasiveness☆

  • Daniel A. Holterman, Ph.D.

      Affiliations

    • Departments of Microbiology and Molecular Cell Biology, Eastern Virginia Medical School, Norfolk, VA 23507, USA
    • Corresponding Author InformationCorresponding author. Tel.: +1-480-355-8128; fax: +1-480-391-7170
    • ,
  • Jose I. Diaz, M.D.

      Affiliations

    • Departments of Microbiology and Molecular Cell Biology, Eastern Virginia Medical School, Norfolk, VA 23507, USA
    • Department of Pathology, Eastern Virginia Medical School, Norfolk, VA 23507, USA
    • ,
  • Peter F. Blackmore, Ph.D.

      Affiliations

    • Department of Physiological Sciences, Eastern Virginia Medical School, Norfolk, VA 23507, USA
    • ,
  • John W. Davis, M.D.

      Affiliations

    • Department of Urology, Eastern Virginia Medical School, Norfolk, VA 23507, USA
    • The Virginia Prostate Center, Eastern Virginia Medical School, Norfolk, VA 23507, USA
    • ,
  • Paul F. Schellhammer, M.D.

      Affiliations

    • Department of Urology, Eastern Virginia Medical School, Norfolk, VA 23507, USA
    • The Virginia Prostate Center, Eastern Virginia Medical School, Norfolk, VA 23507, USA
    • ,
  • Alberto Corica, M.D.

      Affiliations

    • Departments of Microbiology and Molecular Cell Biology, Eastern Virginia Medical School, Norfolk, VA 23507, USA
    • ,
  • Oliver J. Semmes, Ph.D.

      Affiliations

    • Departments of Microbiology and Molecular Cell Biology, Eastern Virginia Medical School, Norfolk, VA 23507, USA
    • The Virginia Prostate Center, Eastern Virginia Medical School, Norfolk, VA 23507, USA
    • ,
  • Antonia Vlahou, Ph.D.

      Affiliations

    • Present address: Division of Biotechnology, Foundation for Biomedical Research of the Academy of Athens, Athens, Greece.
    • Departments of Microbiology and Molecular Cell Biology, Eastern Virginia Medical School, Norfolk, VA 23507, USA

Received 10 February 2005; received in revised form 25 July 2005; accepted 26 July 2005.

Abstract 

Alpha-defensin (α-defensin) has been identified as a potential marker for bladder cancer in urine by surface enhanced laser desorption ionization studies, and confirmed using both immunoabsorption and immunodepletion studies. The objective of this study was to investigate the role of α-defensin in bladder cancer. Immunohistochemical analysis of tissue sections showed that α-defensin peptides are frequently expressed in bladder cancer cells. It is noteworthy that expression of α-defensins increased with tumor invasiveness. Surface enhanced laser desorption ionization analysis showed the presence of α-defensin in the T24 and A498 cancer cell lines. These cell lines show higher classically aggressive in vitro characteristics compared with the J82 cells that did not express α-defensin. Exogenously added α-defensin increased the proliferation and motility/invasiveness of these cell lines using respective assays. It is interesting that α-defensin peptides increased intracellular calcium ions (Ca2+). These data are consistent with a role for α-defensin in bladder cancer via modulation of cell motility and invasiveness using common intracellular signals, such as Ca2+. We propose that autocrine tumor expression of α-defensins may play an important role in facilitating the invasive phenotype of bladder cancer in patients.

Keywords:  Bladder cancer , Transitional cell carcinoma , Cancer invasion , Intracellular calcium

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☆ This work was supported by funds from the 2003 Ladies Auxiliary to Veterans of Foreign Wars Cancer Research Fellowship (D.A.H.), the Elsa U. Pardee Research Foundation (A.V.), and The Early Detection Research Network (O.J.S.).

PII: S1078-1439(05)00203-6

doi:10.1016/j.urolonc.2005.07.010

Urologic Oncology: Seminars and Original Investigations
Volume 24, Issue 2 , Pages 97-108, March 2006

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