PortalPublikationenThe Senescence-associated Secretory Phenotype Mediates Oncog...

The Senescence-associated Secretory Phenotype Mediates Oncogene-induced Senescence in Pediatric Pilocytic Astrocytoma

Standard

The Senescence-associated Secretory Phenotype Mediates Oncogene-induced Senescence in Pediatric Pilocytic Astrocytoma. / Buhl, Juliane L; Selt, Florian; Hielscher, Thomas; Guiho, Romain; Ecker, Jonas; Sahm, Felix; Ridinger, Johannes; Riehl, Dennis; Usta, Diren; Ismer, Britta; Sommerkamp, Alexander C; Martinez-Barbera, J P; Wefers, Annika K; Remke, Marc; Picard, Daniel; Pusch, Stefan; Gronych, Jan; Oehme, Ina; van Tilburg, Cornelis M; Kool, Marcel; Kuhn, Daniela; Capper, David; von Deimling, Andreas; Schuhmann, Martin U; Herold-Mende, Christel; Korshunov, Andrey; Brummer, Tilman; Pfister, Stefan M; Jones, David T W; Witt, Olaf; Milde, Till.

in: CLIN CANCER RES, Jahrgang 25, Nr. 6, 15.03.2019, S. 1851-1866.

Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung

Harvard

Buhl, JL, Selt, F, Hielscher, T, Guiho, R, Ecker, J, Sahm, F, Ridinger, J, Riehl, D, Usta, D, Ismer, B, Sommerkamp, AC, Martinez-Barbera, JP, Wefers, AK, Remke, M, Picard, D, Pusch, S, Gronych, J, Oehme, I, van Tilburg, CM, Kool, M, Kuhn, D, Capper, D, von Deimling, A, Schuhmann, MU, Herold-Mende, C, Korshunov, A, Brummer, T, Pfister, SM, Jones, DTW, Witt, O & Milde, T 2019, 'The Senescence-associated Secretory Phenotype Mediates Oncogene-induced Senescence in Pediatric Pilocytic Astrocytoma', CLIN CANCER RES, Jg. 25, Nr. 6, S. 1851-1866. https://doi.org/10.1158/1078-0432.CCR-18-1965

APA

Buhl, J. L., Selt, F., Hielscher, T., Guiho, R., Ecker, J., Sahm, F., Ridinger, J., Riehl, D., Usta, D., Ismer, B., Sommerkamp, A. C., Martinez-Barbera, J. P., Wefers, A. K., Remke, M., Picard, D., Pusch, S., Gronych, J., Oehme, I., van Tilburg, C. M., ... Milde, T. (2019). The Senescence-associated Secretory Phenotype Mediates Oncogene-induced Senescence in Pediatric Pilocytic Astrocytoma. CLIN CANCER RES, 25(6), 1851-1866. https://doi.org/10.1158/1078-0432.CCR-18-1965

Vancouver

Buhl JL, Selt F, Hielscher T, Guiho R, Ecker J, Sahm F et al. The Senescence-associated Secretory Phenotype Mediates Oncogene-induced Senescence in Pediatric Pilocytic Astrocytoma. CLIN CANCER RES. 2019 Mär 15;25(6):1851-1866. https://doi.org/10.1158/1078-0432.CCR-18-1965

Bibtex

@article{ec0f4cba918440929782249731c5c349,
title = "The Senescence-associated Secretory Phenotype Mediates Oncogene-induced Senescence in Pediatric Pilocytic Astrocytoma",
abstract = "PURPOSE: Pilocytic astrocytoma is the most common childhood brain tumor, characterized by constitutive MAPK activation. MAPK signaling induces oncogene-induced senescence (OIS), which may cause unpredictable growth behavior of pilocytic astrocytomas. The senescence-associated secretory phenotype (SASP) has been shown to regulate OIS, but its role in pilocytic astrocytoma remains unknown.Experimental Design: The patient-derived pilocytic astrocytoma cell culture model, DKFZ-BT66, was used to demonstrate presence of the SASP and analyze its impact on OIS in pilocytic astrocytoma. The model allows for doxycycline-inducible switching between proliferation and OIS. Both states were studied using gene expression profiling (GEP), Western blot, ELISA, and cell viability testing. Primary pilocytic astrocytoma tumors were analyzed by GEP and multiplex assay.RESULTS: SASP factors were upregulated in primary human and murine pilocytic astrocytoma and during OIS in DKFZ-BT66 cells. Conditioned medium induced growth arrest of proliferating pilocytic astrocytoma cells. The SASP factors IL1B and IL6 were upregulated in primary pilocytic astrocytoma, and both pathways were regulated during OIS in DKFZ-BT66. Stimulation with rIL1B but not rIL6 reduced growth of DKFZ-BT66 cells and induced the SASP. Anti-inflammatory treatment with dexamethasone induced regrowth of senescent cells and inhibited the SASP. Senescent DKFZ-BT66 cells responded to senolytic BCL2 inhibitors. High IL1B and SASP expression in pilocytic astrocytoma tumors was associated with favorable progression-free survival.CONCLUSIONS: We provide evidence for the SASP regulating OIS in pediatric pilocytic astrocytoma, with IL1B as a relevant mediator. SASP expression could enable prediction of progression in patients with pilocytic astrocytoma. Further investigation of the SASP driving the unpredictable growth of pilocytic astrocytomas, and its possible therapeutic application, is warranted.",
keywords = "Animals, Astrocytoma/mortality, Brain Neoplasms/mortality, Cell Proliferation, Cellular Senescence, Child, Culture Media, Conditioned/metabolism, Datasets as Topic, Disease Models, Animal, Female, Gene Expression Profiling, Humans, Interleukin-1beta/metabolism, Male, Mice, Primary Cell Culture, Prognosis, Progression-Free Survival, Tumor Cells, Cultured",
author = "Buhl, {Juliane L} and Florian Selt and Thomas Hielscher and Romain Guiho and Jonas Ecker and Felix Sahm and Johannes Ridinger and Dennis Riehl and Diren Usta and Britta Ismer and Sommerkamp, {Alexander C} and Martinez-Barbera, {J P} and Wefers, {Annika K} and Marc Remke and Daniel Picard and Stefan Pusch and Jan Gronych and Ina Oehme and {van Tilburg}, {Cornelis M} and Marcel Kool and Daniela Kuhn and David Capper and {von Deimling}, Andreas and Schuhmann, {Martin U} and Christel Herold-Mende and Andrey Korshunov and Tilman Brummer and Pfister, {Stefan M} and Jones, {David T W} and Olaf Witt and Till Milde",
note = "{\textcopyright}2018 American Association for Cancer Research.",
year = "2019",
month = mar,
day = "15",
doi = "10.1158/1078-0432.CCR-18-1965",
language = "English",
volume = "25",
pages = "1851--1866",
journal = "CLIN CANCER RES",
issn = "1078-0432",
publisher = "American Association for Cancer Research Inc.",
number = "6",

}

RIS

TY - JOUR

T1 - The Senescence-associated Secretory Phenotype Mediates Oncogene-induced Senescence in Pediatric Pilocytic Astrocytoma

AU - Buhl, Juliane L

AU - Selt, Florian

AU - Hielscher, Thomas

AU - Guiho, Romain

AU - Ecker, Jonas

AU - Sahm, Felix

AU - Ridinger, Johannes

AU - Riehl, Dennis

AU - Usta, Diren

AU - Ismer, Britta

AU - Sommerkamp, Alexander C

AU - Martinez-Barbera, J P

AU - Wefers, Annika K

AU - Remke, Marc

AU - Picard, Daniel

AU - Pusch, Stefan

AU - Gronych, Jan

AU - Oehme, Ina

AU - van Tilburg, Cornelis M

AU - Kool, Marcel

AU - Kuhn, Daniela

AU - Capper, David

AU - von Deimling, Andreas

AU - Schuhmann, Martin U

AU - Herold-Mende, Christel

AU - Korshunov, Andrey

AU - Brummer, Tilman

AU - Pfister, Stefan M

AU - Jones, David T W

AU - Witt, Olaf

AU - Milde, Till

N1 - ©2018 American Association for Cancer Research.

PY - 2019/3/15

Y1 - 2019/3/15

N2 - PURPOSE: Pilocytic astrocytoma is the most common childhood brain tumor, characterized by constitutive MAPK activation. MAPK signaling induces oncogene-induced senescence (OIS), which may cause unpredictable growth behavior of pilocytic astrocytomas. The senescence-associated secretory phenotype (SASP) has been shown to regulate OIS, but its role in pilocytic astrocytoma remains unknown.Experimental Design: The patient-derived pilocytic astrocytoma cell culture model, DKFZ-BT66, was used to demonstrate presence of the SASP and analyze its impact on OIS in pilocytic astrocytoma. The model allows for doxycycline-inducible switching between proliferation and OIS. Both states were studied using gene expression profiling (GEP), Western blot, ELISA, and cell viability testing. Primary pilocytic astrocytoma tumors were analyzed by GEP and multiplex assay.RESULTS: SASP factors were upregulated in primary human and murine pilocytic astrocytoma and during OIS in DKFZ-BT66 cells. Conditioned medium induced growth arrest of proliferating pilocytic astrocytoma cells. The SASP factors IL1B and IL6 were upregulated in primary pilocytic astrocytoma, and both pathways were regulated during OIS in DKFZ-BT66. Stimulation with rIL1B but not rIL6 reduced growth of DKFZ-BT66 cells and induced the SASP. Anti-inflammatory treatment with dexamethasone induced regrowth of senescent cells and inhibited the SASP. Senescent DKFZ-BT66 cells responded to senolytic BCL2 inhibitors. High IL1B and SASP expression in pilocytic astrocytoma tumors was associated with favorable progression-free survival.CONCLUSIONS: We provide evidence for the SASP regulating OIS in pediatric pilocytic astrocytoma, with IL1B as a relevant mediator. SASP expression could enable prediction of progression in patients with pilocytic astrocytoma. Further investigation of the SASP driving the unpredictable growth of pilocytic astrocytomas, and its possible therapeutic application, is warranted.

AB - PURPOSE: Pilocytic astrocytoma is the most common childhood brain tumor, characterized by constitutive MAPK activation. MAPK signaling induces oncogene-induced senescence (OIS), which may cause unpredictable growth behavior of pilocytic astrocytomas. The senescence-associated secretory phenotype (SASP) has been shown to regulate OIS, but its role in pilocytic astrocytoma remains unknown.Experimental Design: The patient-derived pilocytic astrocytoma cell culture model, DKFZ-BT66, was used to demonstrate presence of the SASP and analyze its impact on OIS in pilocytic astrocytoma. The model allows for doxycycline-inducible switching between proliferation and OIS. Both states were studied using gene expression profiling (GEP), Western blot, ELISA, and cell viability testing. Primary pilocytic astrocytoma tumors were analyzed by GEP and multiplex assay.RESULTS: SASP factors were upregulated in primary human and murine pilocytic astrocytoma and during OIS in DKFZ-BT66 cells. Conditioned medium induced growth arrest of proliferating pilocytic astrocytoma cells. The SASP factors IL1B and IL6 were upregulated in primary pilocytic astrocytoma, and both pathways were regulated during OIS in DKFZ-BT66. Stimulation with rIL1B but not rIL6 reduced growth of DKFZ-BT66 cells and induced the SASP. Anti-inflammatory treatment with dexamethasone induced regrowth of senescent cells and inhibited the SASP. Senescent DKFZ-BT66 cells responded to senolytic BCL2 inhibitors. High IL1B and SASP expression in pilocytic astrocytoma tumors was associated with favorable progression-free survival.CONCLUSIONS: We provide evidence for the SASP regulating OIS in pediatric pilocytic astrocytoma, with IL1B as a relevant mediator. SASP expression could enable prediction of progression in patients with pilocytic astrocytoma. Further investigation of the SASP driving the unpredictable growth of pilocytic astrocytomas, and its possible therapeutic application, is warranted.

KW - Animals

KW - Astrocytoma/mortality

KW - Brain Neoplasms/mortality

KW - Cell Proliferation

KW - Cellular Senescence

KW - Child

KW - Culture Media, Conditioned/metabolism

KW - Datasets as Topic

KW - Disease Models, Animal

KW - Female

KW - Gene Expression Profiling

KW - Humans

KW - Interleukin-1beta/metabolism

KW - Male

KW - Mice

KW - Primary Cell Culture

KW - Prognosis

KW - Progression-Free Survival

KW - Tumor Cells, Cultured

U2 - 10.1158/1078-0432.CCR-18-1965

DO - 10.1158/1078-0432.CCR-18-1965

M3 - SCORING: Journal article

C2 - 30530705

VL - 25

SP - 1851

EP - 1866

JO - CLIN CANCER RES

JF - CLIN CANCER RES

SN - 1078-0432

IS - 6

ER -