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| Status |
Public on Dec 31, 2014 |
| Title |
METRONOMIC TOPOTECAN CAUSES THERAPY-INDUCED TUMOR CELL SENESCENCE AND LOSS OF AGGRESSIVE PROPERTIES IN MYCN-AMPLIFIED CHILDHOOD CANCER [IN VIVO] |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
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| Summary |
Evidence is accumulating that senescence drives cure in various murine and human malignancies. We demonstrate that metronomic, repetitive low-dose topotecan treatment leads to tumor cell senescence in vitro and in vivo and long-term cure in a model for the aggressive childhood cancer neuroblastoma. By using the senescence-associated secretory phenotype (SASP) as a discriminator for beneficial versus adverse effects of senescence, we identified topotecan as inducer of a favorable SASP. Senescent tumor cells are growth arrested and act growth inhibitory on co-cultured non-senescent tumor cells. MYCN oncogene amplification and expression, hallmarks of aggressive neuroblastoma, are significantly reduced, supporting an initial transition to a more favorable phenotype. These new aspects of metronomic drug treatment are clinically relevant and might apply to other tumor entities.
Keywords: stress response, therapy induced senescence, cellular response, cancer treatment, neuroblastoma
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| Overall design |
In total, 6 samples were analysed: The MYCN amplified neuroblastoma cell line STA-NB-10 was subcutaneously transplanted in T-cell deficient nude mice (Crl:CD1/Foxn1nu/nu), tumors were grown until a mean volume of 0.5 cm3 was reached and treated for 2 weeks with 0.1 mg/kg/d Topotecan i.p., daily. After sacrificing the mice, tumors were immediately prepared, snap frozen at liquid N2 and subsequently stored at -80°C.
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| Contributor(s) |
Taschner-Mandl S, Schwarz M, Blaha J, Hohenegger M, Kauer M, Kromp F, Frank N, Rifatbegovic F, Ambros IM, Ambros PF |
| Citation missing |
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| Submission date |
Jul 10, 2014 |
| Last update date |
Aug 23, 2018 |
| Contact name |
Maximilian Kauer |
| E-mail(s) |
maximilian.kauer@ccri.at
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| Organization name |
CCRI, St.Anna Children Cancer Research Institute
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| Department |
Molecular Biology
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| Lab |
Heinrich Kovar
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| Street address |
Zimmermannplatz 10
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| City |
Vienna |
| ZIP/Postal code |
1090 |
| Country |
Austria |
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| Platforms (1) |
| GPL15207 |
[PrimeView] Affymetrix Human Gene Expression Array |
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| Samples (6)
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| This SubSeries is part of SuperSeries: |
| GSE59298 |
METRONOMIC TOPOTECAN CAUSES THERAPY-INDUCED TUMOR CELL SENESCENCE AND LOSS OF AGGRESSIVE PROPERTIES IN MYCN-AMPLIFIED CHILDHOOD CANCER |
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| Relations |
| BioProject |
PRJNA254982 |
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