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Examination of survivin expression in 50 chordoma specimens--A histological and in vitro study
Elke V Froehlich1, Beate Rinner, Alexander J A Deutsch
1Department of Orthopedic Surgery, Medical University of Graz, Graz, Austria.
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.
Insights
Survivin, a key cell regulator, is overexpressed in chordomas, a rare bone cancer. Targeting survivin with YM155 shows promise for new chordoma therapies by inhibiting tumor growth and inducing cell death.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- Chordomas are slow-growing, destructive tumors of the axial skeleton with poor prognosis.
- Current treatments (surgery, radiotherapy) are limited, highlighting the need for novel therapeutic strategies.
- Survivin, an apoptosis inhibitor, is implicated in various cancers and regulates mitosis.
Purpose of the Study:
- To investigate the role and expression of survivin in chordoma.
- To evaluate survivin as a potential therapeutic target in chordoma.
Main Methods:
- Immunohistochemistry was used to assess survivin expression in 50 chordoma samples and 3 cell lines.
- Correlation of survivin expression with clinical parameters and recurrence.
- In vitro experiments involving survivin knockdown and YM155 treatment on chordoma cell lines.
Main Results:
- Survivin was overexpressed in chordoma samples and cell lines.
- YM155 treatment inhibited chordoma cell growth dose- and time-dependently.
- Survivin knockdown induced G2/M cell cycle arrest, decreased proliferation, polyploidy, and apoptosis.
Conclusions:
- Survivin plays a crucial role in chordoma cell cycle progression.
- Targeting survivin with YM155 represents a promising therapeutic strategy for chordoma.
- Further research into survivin-targeted therapies could improve chordoma treatment outcomes.
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