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J Cancer Metastasis Treat 2016;2 Suppl 1

Key words: our first proof-of-principle study, we could show that
Radiation therapy, cancer stem cells, epigenetic ALDH-positive CSCs are radioresistant and maintained
reprogramming, radiosensitization directly by the Wnt/β-catenin signaling pathway.
[1]
In addition, we found that irradiation is inducing in
References a dose- and time-dependent manner several CSC
marker and CSC properties. This irradiation-induced
1. Peitzsch C, Cojoc M, Hein L, Kurth I, Mäbert K, Trautmann F, Klink CSC-plasticity was attributed to the modulation of
B, Schröck E, Wirth MP, Krause M, Stakhovsky EA, Telegeev GD, the histone methylation code. Within the presented
[2]
Novotny V, Toma M, Muders M, Baretton GB, Frame FM, Maitland
NJ, Baumann M, Dubrovska A. An epigenetic reprogramming study we analyzed a panel of secreted cytokines in
strategy to resensitize radioresistant prostate cancer cells. Cancer Res the medium of the radioresistant sublines and found
2016;76:2637-51. for example the CXCR4-CXCL12 signaling to be
2. Cojoc M, Peitzsch C, Kurth I, Trautmann F, Kunz-Schughart LA, involved in the CSC maintenance and the induction of
Telegeev GD, Stakhovsky EA, Walker JR, Simin K, Lyle S, Fuessel radioresistance in prostate cancer. This was proven in
S, Erdmann K, Wirth MP, Krause M, Baumann M, Dubrovska a s.c. xenotransplantation model in vivo and in ex vivo
A. Aldehyde dehydrogenase is regulated by β-Catenin/TCF and treated primary prostate cancer biopsies. Conclusion:
promotes radioresistance in prostate cancer progenitor cells. Cancer
Res 2015;75:1482-94. The CXCR4-CXCL12 signaling axis is involved in the
3. Krause M, Dubrovska A, Linge A, Baumann M. Cancer stem cells: maintenance of prostate CSCs and is contributing to
radioresistance, prediction of radiotherapy outcome and specific their radioresistant properties.
targets for combined treatments. Adv Drug Deliv Rev 2016 Feb 12.
pii: S0169-409X(16)30052-7. Key words:
Radiotherapy, cancer stem cells, cytokines, plasticity
A14
Cytokine profile involved in the maintenance References
of radioresistant prostate cancer stem cells 1. Peitzsch C, Cojoc M, Hein L, Kurth I, Mäbert K, Trautmann F, Klink
B, Schröck E, Wirth MP, Krause M, Stakhovsky EA, Telegeev GD,
Claudia Peitzsch , Monica Cojoc , Linda Hein , Ina Novotny V, Toma M, Muders M, Baretton GB, Frame FM, Maitland
1
1
1
Kurth , Anna Dubrovska 1,2 NJ, Baumann M, Dubrovska A. An epigenetic reprogramming
1,3
strategy to resensitize radioresistant prostate cancer cells. Cancer Res
1 OncoRay - National Center for Radiation Research in Oncology, Dresden, Germany; 2016;76:2637-51.
2 German Cancer Consortium (DKTK) Dresden, Dresden, Germany;
3 Nationales Centrum für Tumorerkrankungen (NCT) Dresden, Dresden, Germany 2. Cojoc M, Peitzsch C, Kurth I, Trautmann F, Kunz-Schughart LA,
Telegeev GD, Stakhovsky EA, Walker JR, Simin K, Lyle S, Fuessel
S, Erdmann K, Wirth MP, Krause M, Baumann M, Dubrovska
Aim: There is increasing evidence that human prostate A. Aldehyde dehydrogenase is regulated by β-Catenin/TCF and
cancer is driven by a malignant subpopulation with promotes radioresistance in prostate cancer progenitor cells. Cancer
stem-like properties. These cancer stem cells (CSC) Res 2015;75:1482-94.
contribute to tumor-initiation, metastasis, therapy-
resistance and tumor relapse. We hypothesize that A15
the determination of CSC-related biomarker in pre- Oxidative stress, metastasis and melanoma
treatment biopsies of prostate cancer patients is
correlating with treatment outcome and can be used stem cell - in vitro and in vivo analysis
for patient stratification and treatment selection. Telma Lisbôa-Nascimento, Milene Ormanji, Darcy
Methods: We generated isogenic radioresistant Marinho, Michele Longoni Calió, Vera Lúcia Rigoni,
prostate cancer cell lines by applying several fractions Clélia Rejane Antônio-Bertoncini, Alice Teixeira Ferreira,
of 4 Gy over a certain period of time until a total dose Francisco Ribas Bosco
> 56 Gy (RR). These radioresistant sublines exhibit
higher expression of CSC marker (e.g. ALDH, CD133, Federal University of Sao Paulo, Sao Paulo, Brazil
CXCR4, ABCG2), epithelial-to-mesenchymal transition
(EMT) phenotypes, higher self-renewal properties Aim: Cancer stem cells play an essential role to
(sphere-formation), higher tumorigenicity and higher maintain the tumor size or fuel its growth. In an
migratory activity. We applied several comparative- advanced stage of melanoma, the presence of a
omic approaches, such as genomic, proteomic, subpopulation of melanoma stem cells (MSC) is
metabolomic, epigenomic and secretome analysis, reflected in the resistance to the therapies and
comparing aldehyde dehydrogenase (ALDH)-positive development of the metastasis. MSC exhibit an altered
CSCs with the RR sublines to identify novel biomarker metabolism when compared to normal melanocyte.
for prostate cancer radioresistance and to unravel the This alteration increases in the presence of reactive
contributing molecular mechanisms. Results: Within oxygen species (ROS), such as superoxide anion
Journal of Cancer Metastasis and Treatment ¦ Volume 2 ¦ November 16, 2016 425