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Targeting abundant survivin expression in liposarcoma: subtype dependent therapy responses to YM155 treatment
Christian Vay1, Philipp M Schlünder1, Levent Dizdar1
1Department of Surgery (A), Heinrich-Heine-University and University Hospital Duesseldorf, Moorenstr. 5, Bldg. 12.46, 40225, Duesseldorf, Germany.
Purpose:
Liposarcoma (LPS) represent the largest group of malignant soft tissue tumours comprising a heterogeneous group of subtypes in which the degrees of chemoresistance and radiosensitivity strongly vary. Consequently, it is of utmost interest to establish novel therapeutic regimens based on molecular targets.
Methods:
Immunohistochemical staining of survivin was performed in tissue microarrays comprising 49 primary LPS specimens. LPS cell lines were treated with survivin antagonist YM155 and doxorubicin or etoposide alone as well as in combination. Changes in cell viability were investigated and the synergistic effect of a combined therapy analysed.
Results:
Immunohistochemistry revealed an abundant expression of survivin in LPS that significantly concurred with less-differentiated tumour subtypes and grading. In vitro, we demonstrated the impact of the survivin inhibitor YM155 on dedifferentiated LPS (DDLPS) and, even more imposing, pleomorphic LPS (PLS) tumour cell viability with a strong induction of apoptosis. A combined treatment of doxorubicin or etoposide with YM155 augmented the cytotoxic effects on DDLPS and PLS cells.
Conclusion:
These findings support the significant role of survivin in the oncogenesis and progression of LPS subtypes providing a rationale to target survivin in eligible in-vivo models and to pioneer clinical applications of survivin-specific substances unfolding their therapeutic potential in LPS patients prospectively.
Insights
Targeting survivin, a protein abundant in liposarcoma (LPS), with YM155 shows promise. Combined with chemotherapy, it enhances cancer cell death, suggesting new therapeutic strategies for LPS patients.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- Liposarcoma (LPS) is a heterogeneous soft tissue tumor with variable chemo- and radioresistance.
- Identifying molecular targets is crucial for developing novel therapeutic regimens for LPS.
Purpose of the Study:
- To investigate the role of survivin in liposarcoma subtypes.
- To evaluate the efficacy of a survivin antagonist (YM155) as a potential therapeutic agent for LPS.
Main Methods:
- Immunohistochemical staining of survivin in 49 primary LPS specimens.
- In vitro treatment of LPS cell lines with YM155, doxorubicin, or etoposide, alone and in combination.
- Assessment of cell viability and apoptosis induction.
Main Results:
- Survivin expression was abundant in LPS, correlating with less-differentiated subtypes and higher tumor grade.
- YM155 significantly reduced viability and induced apoptosis in dedifferentiated LPS (DDLPS) and pleomorphic LPS (PLS) cell lines.
- Combination therapy of YM155 with doxorubicin or etoposide enhanced cytotoxic effects on DDLPS and PLS cells.
Conclusions:
- Survivin plays a significant role in the oncogenesis and progression of LPS subtypes.
- Targeting survivin presents a promising therapeutic strategy for LPS.
- Further in vivo studies and clinical applications of survivin-specific agents are warranted for LPS patients.
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