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Updated: Aug 10, 2025
Tumorsphere Derivation and Treatment from Primary Tumor Cells Isolated from Mouse Rhabdomyosarcomas
Published on: September 13, 2019
Surfaceome Profiling of Cell Lines and Patient-Derived Xenografts Confirm FGFR4, NCAM1, CD276, and Highlight AGRL2,
Andrea Timpanaro1,2,3, Caroline Piccand1,2,3, Anne-Christine Uldry4
1Department of Pediatric Hematology and Oncology, Inselspital, Bern University Hospital, University of Bern, 3010 Bern, Switzerland.
Abstract:
Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma in children. The prognosis for patients with high-grade and metastatic disease is still very poor, and survivors are burdened with long-lasting side effects. Therefore, more effective and less toxic therapies are needed. Surface proteins are ideal targets for antibody-based therapies, like bispecific antibodies, antibody-drug conjugates, or chimeric antigen receptor (CAR) T-cells. Specific surface targets for RMS are scarce. Here, we performed a surfaceome profiling based on differential centrifugation enrichment of surface/membrane proteins and detection by LC-MS on six fusion-positive (FP) RMS cell lines, five fusion-negative (FN) RMS cell lines, and three RMS patient-derived xenografts (PDXs). A total of 699 proteins were detected in the three RMS groups. Ranking based on expression levels and comparison to expression in normal MRC-5 fibroblasts and myoblasts, followed by statistical analysis, highlighted known RMS targets such as FGFR4, NCAM1, and CD276/B7-H3, and revealed AGRL2, JAM3, MEGF10, GPC4, CADM2, as potential targets for immunotherapies of RMS. L1CAM expression was investigated in RMS tissues, and strong L1CAM expression was observed in more than 80% of alveolar RMS tumors, making it a practicable target for antibody-based therapies of alveolar RMS.
Insights
Researchers identified new surface protein targets for rhabdomyosarcoma (RMS) immunotherapies. L1CAM is a promising target for alveolar RMS, offering hope for more effective and less toxic treatments for this childhood cancer.
Area of Science:
- Oncology
- Immunology
- Biochemistry
Background:
- Rhabdomyosarcoma (RMS) is a prevalent childhood soft tissue sarcoma with poor prognosis for high-grade and metastatic cases.
- Current treatments for RMS can lead to significant long-term side effects in survivors.
- Novel, less toxic therapeutic strategies are urgently required for RMS treatment.
Purpose of the Study:
- To identify novel surface protein targets on RMS cells for antibody-based immunotherapies.
- To compare surface protein expression between RMS cell lines, xenografts, and normal cells.
- To evaluate the potential of identified targets for therapeutic intervention in RMS.
Main Methods:
- Surfaceome profiling using differential centrifugation and LC-MS on RMS cell lines and patient-derived xenografts.
- Differential expression analysis comparing RMS samples to normal fibroblasts and myoblasts.
- Immunohistochemical analysis of L1CAM expression in RMS tumor tissues.
Main Results:
- A total of 699 surface proteins were detected across RMS samples.
- Known RMS targets (FGFR4, NCAM1, CD276/B7-H3) were confirmed.
- Novel potential targets including AGRL2, JAM3, MEGF10, GPC4, CADM2, and L1CAM were identified.
- Strong L1CAM expression (>80%) was observed in alveolar RMS tumors.
Conclusions:
- Surfaceome profiling is effective for identifying RMS-specific targets.
- AGRL2, JAM3, MEGF10, GPC4, CADM2, and L1CAM represent promising targets for RMS immunotherapies.
- L1CAM is a viable therapeutic target for alveolar RMS, warranting further investigation for antibody-based treatments.
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