Examination of survivin expression in 50 chordoma specimens-A histological and in vitro study
- 13 March 2015
- journal article
- Published by Wiley in Journal of Orthopaedic Research
- Vol. 33 (5), 771-778
- https://doi.org/10.1002/jor.22819
Abstract
Chordomas mainly arise along the axial skeleton and are characterized by their slow but destructive growth. Prognosis and quality of life are poor because treatment options are mainly limited to surgery and radiotherapy. Survivin, a member of the apoptosis inhibitor protein family, functions as a key regulator of mitosis and programmed cell death, and is overexpressed in many tumor types. The aim of this study was to determine the role of survivin in chordomas. Survivin expression was investigated in 50 chordoma samples and three chordoma cell lines using immunohistochemistry. The intensity of immunostaining was evaluated in regard to the development of recurrences. The immunohistochemical results were correlated with clinical parameters like gender, age, tumor size, and location and were performed in primary chordomas as well as in recurrent lesions. Furthermore, survivin knockdown experiments on chordoma cell lines were performed. YM155 decreased the growth behavior of chordoma cells dose- and time dependently. Transient knockdown of survivin led to a G2/M arrest, decreased proliferation, consistently induced an increase of polyploidy and morphological changes, and induced apoptosis. The resultant data from this study suggest that survivin plays a cell cycle-progressive role in chordomas. Hence, regulation of survivin by YM155 is a promising new target for the development of new therapeutic drugs.Funding Information
- National Bank of Austria (13459, 14356)
This publication has 27 references indexed in Scilit:
- High expression of survivin in sacral chordomaMedical Oncology, 2013
- Survivin selective inhibitor YM155 induce apoptosis in SK-NEP-1 Wilms tumor cellsBMC Cancer, 2012
- Survivin Is a Viable Target for the Treatment of Malignant Peripheral Nerve Sheath TumorsClinical Cancer Research, 2012
- Survivin inhibition by an interacting recombinant peptide, derived from the human ferritin heavy chain, impedes tumor cell growthZeitschrift für Krebsforschung und Klinische Onkologie, 2012
- The role of epidermal growth factor receptor in chordoma pathogenesis: a potential therapeutic targetThe Journal of Pathology, 2010
- Survivin and IAP proteins in cell-death mechanismsBiochemical Journal, 2010
- Clinical and immunological evaluation of anti-apoptosis protein, survivin-derived peptide vaccine in phase I clinical study for patients with advanced or recurrent breast cancerJournal of Translational Medicine, 2008
- Frequent deletion of the CDKN2A locus in chordoma: analysis of chromosomal imbalances using array comparative genomic hybridisationBritish Journal of Cancer, 2007
- Survivin expression levels as independent predictors of survival for osteosarcoma patientsJournal of Orthopaedic Research, 2006
- ChordomasClinical Orthopaedics and Related Research, 1986