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Loss of SS18-SSX1 Inhibits Viability and Induces Apoptosis in Synovial Sarcoma

  • Symposium: Musculoskeletal Tumor Society 2012 Symposium
  • Published:
Clinical Orthopaedics and Related Research®

Abstract

Background

Most synovial sarcomas contain a chromosomal translocation t(X;18), which results in the formation of an oncoprotein SS18-SSX critical to the viability of synovial sarcoma.

Questions/purposes

We (1) established and characterized three novel synovial sarcoma cell lines and asked (2) whether inhibition of SS18-SSX1 decreases cell viability in these cell lines; and (3) whether reduction in viability after SS18-SSX1 knockdown is caused by apoptosis. After identifying a specific posttranscriptional splice variant in our cell lines, we asked (4) whether this provides a survival benefit in synovial sarcoma.

Methods

Cells lines were characterized. SS18-SSX1 knockdown was achieved using a shRNA system. Cell viability was assessed by WST-1 analysis and apoptosis examined by caspase-3 activity.

Results

We confirmed the SS18-SSX1 translocation in all cell lines and identified a consistent splicing variant. We achieved successful knockdown of SS18-SSX1 and with this saw a significant reduction in cell viability. Decreased viability was a result of increased apoptosis. Reintroduction of the exon 8 sequence into cells reduced cell viability in all cell lines.

Conclusions

We confirmed the presence of the SS18-SSX1 translocation in our cell lines and its importance in the survival of synovial sarcoma. We have also demonstrated that reduction in cell viability is related to an increase in apoptosis. In addition, we have identified a potential mediator of SS18-SSX function in exon 8.

Clinical Relevance

SS18-SSX represents a tumor-specific target in synovial sarcoma. Exploitation of SS18-SSX and its protein partners will allow us to develop potent tumor-specific therapeutic agents.

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Acknowledgments

We acknowledge Felasfa M. Wodajo MD, for providing tumor samples from which two of the cell lines were started.

Author information

Authors and Affiliations

  1. MedStar Georgetown Orthopaedic Institute, 110 Irving Street, NW C-2173, Washington, DC, 20010, USA

    Emily E. Carmody Soni MD

  2. Department of Oncology, Lombardi Comprehensive Cancer Institute, Washington, DC, USA

    Emily E. Carmody Soni MD, Silke Schlottman PhD, Hayriye V. Erkizan PhD, Aykut Uren MD & Jeffrey A. Toretsky MD

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  1. Emily E. Carmody Soni MD
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  2. Silke Schlottman PhD
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Corresponding author

Correspondence to Emily E. Carmody Soni MD.

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Each author certifies that he or she, or a member of his or her immediate family, has no funding or commercial associations (eg, consultancies, stock ownership, equity interest, patent/licensing arrangements, etc) that might pose a conflict of interest in connection with the submitted article.

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Each author certifies that his or her institution approved the human protocol for this investigation, that all investigations were conducted in conformity with ethical principles of research, and that informed consent for participation in the study was obtained.

This work was performed at the Lombardi Comprehensive Cancer Institute, Washington, DC, USA.

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Carmody Soni, E.E., Schlottman, S., Erkizan, H.V. et al. Loss of SS18-SSX1 Inhibits Viability and Induces Apoptosis in Synovial Sarcoma. Clin Orthop Relat Res 472, 874–882 (2014). https://doi.org/10.1007/s11999-013-3065-9

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  • DOI: https://doi.org/10.1007/s11999-013-3065-9

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