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Updated: May 3, 2026
Tumorsphere Derivation and Treatment from Primary Tumor Cells Isolated from Mouse Rhabdomyosarcomas
Published on: September 13, 2019
Survivin-responsive conditionally replicating adenovirus kills rhabdomyosarcoma stem cells more efficiently than
Kiyonori Tanoue, Yuqing Wang, Minako Ikeda
1Department of Gene Therapy and Regenerative Medicine, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan. kosai@m2.kufm.kagoshima-u.ac.jp.
Background:
Effective methods for eradicating cancer stem cells (CSCs), which are highly tumorigenic and resistant to conventional therapies, are urgently needed. Our previous studies demonstrated that survivin-responsive conditionally replicating adenoviruses regulated with multiple factors (Surv.m-CRAs), which selectively replicate in and kill a broad range of cancer-cell types, are promising anticancer agents. Here we examined the therapeutic potentials of a Surv.m-CRA against rhabdomyosarcoma stem cells (RSCs), in order to assess its clinical effectiveness and usefulness.
Methods:
Our previous study demonstrated that fibroblast growth factor receptor 3 (FGFR3) is a marker of RSCs. We examined survivin mRNA levels, survivin promoter activities, relative cytotoxicities of Surv.m-CRA in RSC-enriched (serum-minus) vs. RSC-exiguous (serum-plus) and FGFR3-positive vs. FGFR3-negative sorted rhabdomyosarcoma cells, and the in vivo therapeutic effects of Surv.m-CRAs on subcutaneous tumors in mice.
Results:
Both survivin mRNA levels and survivin promoter activities were significantly elevated under RSC-enriched relative to RSC-exiguous culture conditions, and the elevation was more prominent in FGFR3-positive vs. FGFR3-negative sorted cells than in RSC-enriched vs. RSC-exiguous conditions. Although Surv.m-CRA efficiently replicated and potently induced cell death in all populations of rhabdomyosarcoma cells, the cytotoxic effects were more pronounced in RSC-enriched or RSC-purified cells than in RSC-exiguous or progeny-purified cells. Injections of Surv.m-CRAs into tumor nodules generated by transplanting RSC-enriched cells induced significant death of rhabdomyosarcoma cells and regression of tumor nodules.
Conclusions:
The unique therapeutic features of Surv.m-CRA, i.e., not only its therapeutic effectiveness against all cell populations but also its increased effectiveness against CSCs, suggest that Surv.m-CRA is promising anticancer agent.
Insights
Survivin-responsive conditionally replicating adenoviruses (Surv.m-CRAs) show promise in eradicating rhabdomyosarcoma stem cells (RSCs). This therapy is effective against all cancer cells, with enhanced activity against CSCs.
Area of Science:
- Oncolytic virology
- Cancer stem cell biology
- Gene therapy
Background:
- Cancer stem cells (CSCs) are crucial for tumor growth and therapy resistance.
- Survivin-responsive conditionally replicating adenoviruses (Surv.m-CRAs) demonstrate selective cancer cell replication and killing.
- Rhabdomyosarcoma stem cells (RSCs) are a specific target for novel therapeutic strategies.
Purpose of the Study:
- To evaluate the therapeutic potential of Surv.m-CRA against rhabdomyosarcoma stem cells (RSCs).
- To assess the clinical effectiveness and utility of Surv.m-CRA in rhabdomyosarcoma treatment.
Main Methods:
- Investigated survivin mRNA levels and promoter activity in RSC-enriched vs. RSC-exiguous cells.
- Assessed relative cytotoxicity of Surv.m-CRA in sorted FGFR3-positive vs. FGFR3-negative rhabdomyosarcoma cells.
- Evaluated in vivo therapeutic effects of Surv.m-CRAs on subcutaneous rhabdomyosarcoma tumors in mice.
Main Results:
- Survivin expression was elevated in RSC-enriched and FGFR3-positive cells.
- Surv.m-CRA exhibited potent cytotoxicity against all rhabdomyosarcoma cell populations, with enhanced effects on RSCs.
- In vivo administration of Surv.m-CRAs led to significant tumor cell death and regression of rhabdomyosarcoma tumors.
Conclusions:
- Surv.m-CRA demonstrates therapeutic effectiveness against all rhabdomyosarcoma cell populations.
- Surv.m-CRA exhibits increased efficacy against cancer stem cells (CSCs), highlighting its potential as an anticancer agent.
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