Survivin is a potential mediator of prostate cancer metastasis

Min Zhang, John J. Coen, Yoshiyuki Suzuki, Michael R. Siedow, Andrzej Niemierko, Li Yan Khor, Alan Pollack, Yifen Zhang, Anthony L. Zietman, William U. Shipley, Arnab Chakravarti

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39 Scopus citations

Abstract

Purpose: We examined whether Survivin expression is associated with an increased risk of metastasis in prostate cancer. Methods and Materials: A total of 205 patients with T1 (23%) and T2 (77%) prostate cancer were treated with conventional external beam radiation therapy from 1991 to 1993 at the Massachusetts General Hospital. Of the patients, 62 had adequate and suitable-stained tumor material for Survivin analysis. Median follow-up was 102 months (range, 5-127 months). Distant failure was determined on the basis of clinical criteria. In preclinical studies, replication-deficient adenovirus encoding phosphorylation-defective Survivin Thr34→Ala dominant-negative mutant pAd-S(T34A) or short hairpin RNA (shRNA) was used to inhibit Survivin in prostate cancer models, and the cell motility, morphology, and metastasis were investigated. Results: Our correlative data on men with early-stage (T1/T2) prostate cancers treated at Massachusetts General Hospital by definitive radiotherapy indicated that overexpression of Survivin (positive staining in ≥10% cells) was associated with a significantly increased risk for the subsequent development of distant metastasis (p = 0.016) in the univariate analysis. In the multivariate analysis, overexpression of Survivin remained an independent predictor of distant metastasis (p = 0.008). The inhibition of Survivin dramatically inhibited invasiveness of prostate cancer cells in the in vitro invasion assay and spontaneous metastasis in the Dunning prostate cancer in vivo model. Furthermore, attenuation of Survivin resulted in changes in the microtubule cytoskeleton, loss of cellular polarity, and loss of motility. Conclusions: This study suggests that Survivin may be a potentially important prognostic marker and promising therapeutic target in metastatic prostate cancer.

Original languageEnglish (US)
Pages (from-to)1095-1103
Number of pages9
JournalInternational Journal of Radiation Oncology Biology Physics
Volume78
Issue number4
DOIs
StatePublished - Nov 4 2010

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Keywords

  • Metastasis
  • Prostate cancer
  • Survivin

ASJC Scopus subject areas

  • Oncology
  • Radiology Nuclear Medicine and imaging
  • Radiation
  • Cancer Research

Cite this

Zhang, M., Coen, J. J., Suzuki, Y., Siedow, M. R., Niemierko, A., Khor, L. Y., Pollack, A., Zhang, Y., Zietman, A. L., Shipley, W. U., & Chakravarti, A. (2010). Survivin is a potential mediator of prostate cancer metastasis. International Journal of Radiation Oncology Biology Physics, 78(4), 1095-1103. https://doi.org/10.1016/j.ijrobp.2009.09.007