Targeting epigenetic features in clear cell sarcomas based on patient-derived cell lines

Background Clear cell sarcomas (CCSs) are translocated aggressive malignancies, most commonly affecting young adults with a high incidence of metastases and a poor prognosis. Research into the disease is more feasible when adequate models are available. By establishing CCS cell lines from a primary and metastatic lesion and isolating healthy fibroblasts from the same patient, the in vivo process is accurately reflected and aspects of clinical multistep carcinogenesis recapitulated. Methods Isolated tumor cells and normal healthy skin fibroblasts from the same patient were compared in terms of growth behavior and morphological characteristics using light and electron microscopy. Tumorigenicity potential was determined by soft agar colony formation assay and in vivo xenograft applications. While genetic differences between the two lineages were examined by copy number alternation profiles, nuclear magnetic resonance spectroscopy determined arginine methylation as epigenetic features. Potential anti-tumor effects of a protein arginine n-methyltransferase type I (PRMT1) inhibitor were elicited in 2D and 3D cell culture experiments using cell viability and apoptosis assays. Statistical significance was calculated by one-way ANOVA and unpaired t-test. Results The two established CCS cell lines named MUG Lucifer prim and MUG Lucifer met showed differences in morphology, genetic and epigenetic data, reflecting the respective original tissue. The detailed cell line characterization especially in regards to the epigenetic domain allows investigation of new innovative therapies. Based on the epigenetic data, a PRMT1 inhibitor was used to demonstrate the targeted antitumor effect; normal tissue cells isolated and immortalized from the same patient were not affected with the $ IC_{50} $ used. Conclusions MUG Lucifer prim, MUG Lucifer met and isolated and immortalized fibroblasts from the same patient represent an ideal in vitro model to explore the biology of CCS. Based on this cell culture model, novel therapies could be tested in the form of PRMT1 inhibitors, which drive tumor cells into apoptosis, but show no effect on fibroblasts, further supporting their potential as promising treatment options in the combat against CCS. The data substantiate the importance of tailored therapies in the advanced metastatic stage of CCS. Ausführliche Beschreibung

Gespeichert in:

Autor*in:	Karner, Christina [verfasserIn] Anders, Ines Vejzovic, Djenana Szkandera, Joanna Scheipl, Susanne Deutsch, Alexander J. A. Weiss, Larissa Vierlinger, Klemens Kolb, Dagmar Kühberger, Stefan Heitzer, Ellen Habisch, Hansjörg Zhang, Fangrong Madl, Tobias Reininger-Gutmann, Birgit Liegl-Atzwanger, Bernadette Rinner, Beate

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2023

Schlagwörter:	Clear cell sarcoma Metastases Epigenetic hall marks Arginine methylation

Anmerkung:	© The Author(s) 2023

Übergeordnetes Werk:	Enthalten in: Journal of translational medicine - London : BioMed Central, 2003, 21(2023), 1 vom: 29. Jan.
Übergeordnetes Werk:	volume:21 ; year:2023 ; number:1 ; day:29 ; month:01

Links:	Volltext

DOI / URN:	10.1186/s12967-022-03843-4

Katalog-ID:	SPR05139877X

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520			\|a Background Clear cell sarcomas (CCSs) are translocated aggressive malignancies, most commonly affecting young adults with a high incidence of metastases and a poor prognosis. Research into the disease is more feasible when adequate models are available. By establishing CCS cell lines from a primary and metastatic lesion and isolating healthy fibroblasts from the same patient, the in vivo process is accurately reflected and aspects of clinical multistep carcinogenesis recapitulated. Methods Isolated tumor cells and normal healthy skin fibroblasts from the same patient were compared in terms of growth behavior and morphological characteristics using light and electron microscopy. Tumorigenicity potential was determined by soft agar colony formation assay and in vivo xenograft applications. While genetic differences between the two lineages were examined by copy number alternation profiles, nuclear magnetic resonance spectroscopy determined arginine methylation as epigenetic features. Potential anti-tumor effects of a protein arginine n-methyltransferase type I (PRMT1) inhibitor were elicited in 2D and 3D cell culture experiments using cell viability and apoptosis assays. Statistical significance was calculated by one-way ANOVA and unpaired t-test. Results The two established CCS cell lines named MUG Lucifer prim and MUG Lucifer met showed differences in morphology, genetic and epigenetic data, reflecting the respective original tissue. The detailed cell line characterization especially in regards to the epigenetic domain allows investigation of new innovative therapies. Based on the epigenetic data, a PRMT1 inhibitor was used to demonstrate the targeted antitumor effect; normal tissue cells isolated and immortalized from the same patient were not affected with the $ IC_{50} $ used. Conclusions MUG Lucifer prim, MUG Lucifer met and isolated and immortalized fibroblasts from the same patient represent an ideal in vitro model to explore the biology of CCS. Based on this cell culture model, novel therapies could be tested in the form of PRMT1 inhibitors, which drive tumor cells into apoptosis, but show no effect on fibroblasts, further supporting their potential as promising treatment options in the combat against CCS. The data substantiate the importance of tailored therapies in the advanced metastatic stage of CCS.
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allfields	10.1186/s12967-022-03843-4 doi (DE-627)SPR05139877X (SPR)s12967-022-03843-4-e DE-627 ger DE-627 rakwb eng Karner, Christina verfasserin aut Targeting epigenetic features in clear cell sarcomas based on patient-derived cell lines 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2023 Background Clear cell sarcomas (CCSs) are translocated aggressive malignancies, most commonly affecting young adults with a high incidence of metastases and a poor prognosis. Research into the disease is more feasible when adequate models are available. By establishing CCS cell lines from a primary and metastatic lesion and isolating healthy fibroblasts from the same patient, the in vivo process is accurately reflected and aspects of clinical multistep carcinogenesis recapitulated. Methods Isolated tumor cells and normal healthy skin fibroblasts from the same patient were compared in terms of growth behavior and morphological characteristics using light and electron microscopy. Tumorigenicity potential was determined by soft agar colony formation assay and in vivo xenograft applications. While genetic differences between the two lineages were examined by copy number alternation profiles, nuclear magnetic resonance spectroscopy determined arginine methylation as epigenetic features. Potential anti-tumor effects of a protein arginine n-methyltransferase type I (PRMT1) inhibitor were elicited in 2D and 3D cell culture experiments using cell viability and apoptosis assays. Statistical significance was calculated by one-way ANOVA and unpaired t-test. Results The two established CCS cell lines named MUG Lucifer prim and MUG Lucifer met showed differences in morphology, genetic and epigenetic data, reflecting the respective original tissue. The detailed cell line characterization especially in regards to the epigenetic domain allows investigation of new innovative therapies. Based on the epigenetic data, a PRMT1 inhibitor was used to demonstrate the targeted antitumor effect; normal tissue cells isolated and immortalized from the same patient were not affected with the $ IC_{50} $ used. Conclusions MUG Lucifer prim, MUG Lucifer met and isolated and immortalized fibroblasts from the same patient represent an ideal in vitro model to explore the biology of CCS. Based on this cell culture model, novel therapies could be tested in the form of PRMT1 inhibitors, which drive tumor cells into apoptosis, but show no effect on fibroblasts, further supporting their potential as promising treatment options in the combat against CCS. The data substantiate the importance of tailored therapies in the advanced metastatic stage of CCS. Clear cell sarcoma (dpeaa)DE-He213 Metastases (dpeaa)DE-He213 Epigenetic hall marks (dpeaa)DE-He213 Arginine methylation (dpeaa)DE-He213 Anders, Ines aut Vejzovic, Djenana aut Szkandera, Joanna aut Scheipl, Susanne aut Deutsch, Alexander J. A. aut Weiss, Larissa aut Vierlinger, Klemens aut Kolb, Dagmar aut Kühberger, Stefan aut Heitzer, Ellen aut Habisch, Hansjörg aut Zhang, Fangrong aut Madl, Tobias aut Reininger-Gutmann, Birgit aut Liegl-Atzwanger, Bernadette aut Rinner, Beate (orcid)0000-0002-6340-4905 aut Enthalten in Journal of translational medicine London : BioMed Central, 2003 21(2023), 1 vom: 29. Jan. (DE-627)369084136 (DE-600)2118570-0 1479-5876 nnns volume:21 year:2023 number:1 day:29 month:01 https://dx.doi.org/10.1186/s12967-022-03843-4 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 21 2023 1 29 01
spelling	10.1186/s12967-022-03843-4 doi (DE-627)SPR05139877X (SPR)s12967-022-03843-4-e DE-627 ger DE-627 rakwb eng Karner, Christina verfasserin aut Targeting epigenetic features in clear cell sarcomas based on patient-derived cell lines 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2023 Background Clear cell sarcomas (CCSs) are translocated aggressive malignancies, most commonly affecting young adults with a high incidence of metastases and a poor prognosis. Research into the disease is more feasible when adequate models are available. By establishing CCS cell lines from a primary and metastatic lesion and isolating healthy fibroblasts from the same patient, the in vivo process is accurately reflected and aspects of clinical multistep carcinogenesis recapitulated. Methods Isolated tumor cells and normal healthy skin fibroblasts from the same patient were compared in terms of growth behavior and morphological characteristics using light and electron microscopy. Tumorigenicity potential was determined by soft agar colony formation assay and in vivo xenograft applications. While genetic differences between the two lineages were examined by copy number alternation profiles, nuclear magnetic resonance spectroscopy determined arginine methylation as epigenetic features. Potential anti-tumor effects of a protein arginine n-methyltransferase type I (PRMT1) inhibitor were elicited in 2D and 3D cell culture experiments using cell viability and apoptosis assays. Statistical significance was calculated by one-way ANOVA and unpaired t-test. Results The two established CCS cell lines named MUG Lucifer prim and MUG Lucifer met showed differences in morphology, genetic and epigenetic data, reflecting the respective original tissue. The detailed cell line characterization especially in regards to the epigenetic domain allows investigation of new innovative therapies. Based on the epigenetic data, a PRMT1 inhibitor was used to demonstrate the targeted antitumor effect; normal tissue cells isolated and immortalized from the same patient were not affected with the $ IC_{50} $ used. Conclusions MUG Lucifer prim, MUG Lucifer met and isolated and immortalized fibroblasts from the same patient represent an ideal in vitro model to explore the biology of CCS. Based on this cell culture model, novel therapies could be tested in the form of PRMT1 inhibitors, which drive tumor cells into apoptosis, but show no effect on fibroblasts, further supporting their potential as promising treatment options in the combat against CCS. The data substantiate the importance of tailored therapies in the advanced metastatic stage of CCS. Clear cell sarcoma (dpeaa)DE-He213 Metastases (dpeaa)DE-He213 Epigenetic hall marks (dpeaa)DE-He213 Arginine methylation (dpeaa)DE-He213 Anders, Ines aut Vejzovic, Djenana aut Szkandera, Joanna aut Scheipl, Susanne aut Deutsch, Alexander J. A. aut Weiss, Larissa aut Vierlinger, Klemens aut Kolb, Dagmar aut Kühberger, Stefan aut Heitzer, Ellen aut Habisch, Hansjörg aut Zhang, Fangrong aut Madl, Tobias aut Reininger-Gutmann, Birgit aut Liegl-Atzwanger, Bernadette aut Rinner, Beate (orcid)0000-0002-6340-4905 aut Enthalten in Journal of translational medicine London : BioMed Central, 2003 21(2023), 1 vom: 29. Jan. (DE-627)369084136 (DE-600)2118570-0 1479-5876 nnns volume:21 year:2023 number:1 day:29 month:01 https://dx.doi.org/10.1186/s12967-022-03843-4 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 21 2023 1 29 01
allfields_unstemmed	10.1186/s12967-022-03843-4 doi (DE-627)SPR05139877X (SPR)s12967-022-03843-4-e DE-627 ger DE-627 rakwb eng Karner, Christina verfasserin aut Targeting epigenetic features in clear cell sarcomas based on patient-derived cell lines 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2023 Background Clear cell sarcomas (CCSs) are translocated aggressive malignancies, most commonly affecting young adults with a high incidence of metastases and a poor prognosis. Research into the disease is more feasible when adequate models are available. By establishing CCS cell lines from a primary and metastatic lesion and isolating healthy fibroblasts from the same patient, the in vivo process is accurately reflected and aspects of clinical multistep carcinogenesis recapitulated. Methods Isolated tumor cells and normal healthy skin fibroblasts from the same patient were compared in terms of growth behavior and morphological characteristics using light and electron microscopy. Tumorigenicity potential was determined by soft agar colony formation assay and in vivo xenograft applications. While genetic differences between the two lineages were examined by copy number alternation profiles, nuclear magnetic resonance spectroscopy determined arginine methylation as epigenetic features. Potential anti-tumor effects of a protein arginine n-methyltransferase type I (PRMT1) inhibitor were elicited in 2D and 3D cell culture experiments using cell viability and apoptosis assays. Statistical significance was calculated by one-way ANOVA and unpaired t-test. Results The two established CCS cell lines named MUG Lucifer prim and MUG Lucifer met showed differences in morphology, genetic and epigenetic data, reflecting the respective original tissue. The detailed cell line characterization especially in regards to the epigenetic domain allows investigation of new innovative therapies. Based on the epigenetic data, a PRMT1 inhibitor was used to demonstrate the targeted antitumor effect; normal tissue cells isolated and immortalized from the same patient were not affected with the $ IC_{50} $ used. Conclusions MUG Lucifer prim, MUG Lucifer met and isolated and immortalized fibroblasts from the same patient represent an ideal in vitro model to explore the biology of CCS. Based on this cell culture model, novel therapies could be tested in the form of PRMT1 inhibitors, which drive tumor cells into apoptosis, but show no effect on fibroblasts, further supporting their potential as promising treatment options in the combat against CCS. The data substantiate the importance of tailored therapies in the advanced metastatic stage of CCS. Clear cell sarcoma (dpeaa)DE-He213 Metastases (dpeaa)DE-He213 Epigenetic hall marks (dpeaa)DE-He213 Arginine methylation (dpeaa)DE-He213 Anders, Ines aut Vejzovic, Djenana aut Szkandera, Joanna aut Scheipl, Susanne aut Deutsch, Alexander J. A. aut Weiss, Larissa aut Vierlinger, Klemens aut Kolb, Dagmar aut Kühberger, Stefan aut Heitzer, Ellen aut Habisch, Hansjörg aut Zhang, Fangrong aut Madl, Tobias aut Reininger-Gutmann, Birgit aut Liegl-Atzwanger, Bernadette aut Rinner, Beate (orcid)0000-0002-6340-4905 aut Enthalten in Journal of translational medicine London : BioMed Central, 2003 21(2023), 1 vom: 29. Jan. (DE-627)369084136 (DE-600)2118570-0 1479-5876 nnns volume:21 year:2023 number:1 day:29 month:01 https://dx.doi.org/10.1186/s12967-022-03843-4 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 21 2023 1 29 01
allfieldsGer	10.1186/s12967-022-03843-4 doi (DE-627)SPR05139877X (SPR)s12967-022-03843-4-e DE-627 ger DE-627 rakwb eng Karner, Christina verfasserin aut Targeting epigenetic features in clear cell sarcomas based on patient-derived cell lines 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2023 Background Clear cell sarcomas (CCSs) are translocated aggressive malignancies, most commonly affecting young adults with a high incidence of metastases and a poor prognosis. Research into the disease is more feasible when adequate models are available. By establishing CCS cell lines from a primary and metastatic lesion and isolating healthy fibroblasts from the same patient, the in vivo process is accurately reflected and aspects of clinical multistep carcinogenesis recapitulated. Methods Isolated tumor cells and normal healthy skin fibroblasts from the same patient were compared in terms of growth behavior and morphological characteristics using light and electron microscopy. Tumorigenicity potential was determined by soft agar colony formation assay and in vivo xenograft applications. While genetic differences between the two lineages were examined by copy number alternation profiles, nuclear magnetic resonance spectroscopy determined arginine methylation as epigenetic features. Potential anti-tumor effects of a protein arginine n-methyltransferase type I (PRMT1) inhibitor were elicited in 2D and 3D cell culture experiments using cell viability and apoptosis assays. Statistical significance was calculated by one-way ANOVA and unpaired t-test. Results The two established CCS cell lines named MUG Lucifer prim and MUG Lucifer met showed differences in morphology, genetic and epigenetic data, reflecting the respective original tissue. The detailed cell line characterization especially in regards to the epigenetic domain allows investigation of new innovative therapies. Based on the epigenetic data, a PRMT1 inhibitor was used to demonstrate the targeted antitumor effect; normal tissue cells isolated and immortalized from the same patient were not affected with the $ IC_{50} $ used. Conclusions MUG Lucifer prim, MUG Lucifer met and isolated and immortalized fibroblasts from the same patient represent an ideal in vitro model to explore the biology of CCS. Based on this cell culture model, novel therapies could be tested in the form of PRMT1 inhibitors, which drive tumor cells into apoptosis, but show no effect on fibroblasts, further supporting their potential as promising treatment options in the combat against CCS. The data substantiate the importance of tailored therapies in the advanced metastatic stage of CCS. Clear cell sarcoma (dpeaa)DE-He213 Metastases (dpeaa)DE-He213 Epigenetic hall marks (dpeaa)DE-He213 Arginine methylation (dpeaa)DE-He213 Anders, Ines aut Vejzovic, Djenana aut Szkandera, Joanna aut Scheipl, Susanne aut Deutsch, Alexander J. A. aut Weiss, Larissa aut Vierlinger, Klemens aut Kolb, Dagmar aut Kühberger, Stefan aut Heitzer, Ellen aut Habisch, Hansjörg aut Zhang, Fangrong aut Madl, Tobias aut Reininger-Gutmann, Birgit aut Liegl-Atzwanger, Bernadette aut Rinner, Beate (orcid)0000-0002-6340-4905 aut Enthalten in Journal of translational medicine London : BioMed Central, 2003 21(2023), 1 vom: 29. Jan. (DE-627)369084136 (DE-600)2118570-0 1479-5876 nnns volume:21 year:2023 number:1 day:29 month:01 https://dx.doi.org/10.1186/s12967-022-03843-4 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 21 2023 1 29 01
allfieldsSound	10.1186/s12967-022-03843-4 doi (DE-627)SPR05139877X (SPR)s12967-022-03843-4-e DE-627 ger DE-627 rakwb eng Karner, Christina verfasserin aut Targeting epigenetic features in clear cell sarcomas based on patient-derived cell lines 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2023 Background Clear cell sarcomas (CCSs) are translocated aggressive malignancies, most commonly affecting young adults with a high incidence of metastases and a poor prognosis. Research into the disease is more feasible when adequate models are available. By establishing CCS cell lines from a primary and metastatic lesion and isolating healthy fibroblasts from the same patient, the in vivo process is accurately reflected and aspects of clinical multistep carcinogenesis recapitulated. Methods Isolated tumor cells and normal healthy skin fibroblasts from the same patient were compared in terms of growth behavior and morphological characteristics using light and electron microscopy. Tumorigenicity potential was determined by soft agar colony formation assay and in vivo xenograft applications. While genetic differences between the two lineages were examined by copy number alternation profiles, nuclear magnetic resonance spectroscopy determined arginine methylation as epigenetic features. Potential anti-tumor effects of a protein arginine n-methyltransferase type I (PRMT1) inhibitor were elicited in 2D and 3D cell culture experiments using cell viability and apoptosis assays. Statistical significance was calculated by one-way ANOVA and unpaired t-test. Results The two established CCS cell lines named MUG Lucifer prim and MUG Lucifer met showed differences in morphology, genetic and epigenetic data, reflecting the respective original tissue. The detailed cell line characterization especially in regards to the epigenetic domain allows investigation of new innovative therapies. Based on the epigenetic data, a PRMT1 inhibitor was used to demonstrate the targeted antitumor effect; normal tissue cells isolated and immortalized from the same patient were not affected with the $ IC_{50} $ used. Conclusions MUG Lucifer prim, MUG Lucifer met and isolated and immortalized fibroblasts from the same patient represent an ideal in vitro model to explore the biology of CCS. Based on this cell culture model, novel therapies could be tested in the form of PRMT1 inhibitors, which drive tumor cells into apoptosis, but show no effect on fibroblasts, further supporting their potential as promising treatment options in the combat against CCS. The data substantiate the importance of tailored therapies in the advanced metastatic stage of CCS. Clear cell sarcoma (dpeaa)DE-He213 Metastases (dpeaa)DE-He213 Epigenetic hall marks (dpeaa)DE-He213 Arginine methylation (dpeaa)DE-He213 Anders, Ines aut Vejzovic, Djenana aut Szkandera, Joanna aut Scheipl, Susanne aut Deutsch, Alexander J. A. aut Weiss, Larissa aut Vierlinger, Klemens aut Kolb, Dagmar aut Kühberger, Stefan aut Heitzer, Ellen aut Habisch, Hansjörg aut Zhang, Fangrong aut Madl, Tobias aut Reininger-Gutmann, Birgit aut Liegl-Atzwanger, Bernadette aut Rinner, Beate (orcid)0000-0002-6340-4905 aut Enthalten in Journal of translational medicine London : BioMed Central, 2003 21(2023), 1 vom: 29. Jan. (DE-627)369084136 (DE-600)2118570-0 1479-5876 nnns volume:21 year:2023 number:1 day:29 month:01 https://dx.doi.org/10.1186/s12967-022-03843-4 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 21 2023 1 29 01
language	English
source	Enthalten in Journal of translational medicine 21(2023), 1 vom: 29. Jan. volume:21 year:2023 number:1 day:29 month:01
sourceStr	Enthalten in Journal of translational medicine 21(2023), 1 vom: 29. Jan. volume:21 year:2023 number:1 day:29 month:01
format_phy_str_mv	Article
institution	findex.gbv.de
topic_facet	Clear cell sarcoma Metastases Epigenetic hall marks Arginine methylation
isfreeaccess_bool	true
container_title	Journal of translational medicine
authorswithroles_txt_mv	Karner, Christina @@aut@@ Anders, Ines @@aut@@ Vejzovic, Djenana @@aut@@ Szkandera, Joanna @@aut@@ Scheipl, Susanne @@aut@@ Deutsch, Alexander J. A. @@aut@@ Weiss, Larissa @@aut@@ Vierlinger, Klemens @@aut@@ Kolb, Dagmar @@aut@@ Kühberger, Stefan @@aut@@ Heitzer, Ellen @@aut@@ Habisch, Hansjörg @@aut@@ Zhang, Fangrong @@aut@@ Madl, Tobias @@aut@@ Reininger-Gutmann, Birgit @@aut@@ Liegl-Atzwanger, Bernadette @@aut@@ Rinner, Beate @@aut@@
publishDateDaySort_date	2023-01-29T00:00:00Z
hierarchy_top_id	369084136
id	SPR05139877X
language_de	englisch
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Research into the disease is more feasible when adequate models are available. By establishing CCS cell lines from a primary and metastatic lesion and isolating healthy fibroblasts from the same patient, the in vivo process is accurately reflected and aspects of clinical multistep carcinogenesis recapitulated. Methods Isolated tumor cells and normal healthy skin fibroblasts from the same patient were compared in terms of growth behavior and morphological characteristics using light and electron microscopy. Tumorigenicity potential was determined by soft agar colony formation assay and in vivo xenograft applications. While genetic differences between the two lineages were examined by copy number alternation profiles, nuclear magnetic resonance spectroscopy determined arginine methylation as epigenetic features. Potential anti-tumor effects of a protein arginine n-methyltransferase type I (PRMT1) inhibitor were elicited in 2D and 3D cell culture experiments using cell viability and apoptosis assays. Statistical significance was calculated by one-way ANOVA and unpaired t-test. Results The two established CCS cell lines named MUG Lucifer prim and MUG Lucifer met showed differences in morphology, genetic and epigenetic data, reflecting the respective original tissue. The detailed cell line characterization especially in regards to the epigenetic domain allows investigation of new innovative therapies. Based on the epigenetic data, a PRMT1 inhibitor was used to demonstrate the targeted antitumor effect; normal tissue cells isolated and immortalized from the same patient were not affected with the $ IC_{50} $ used. Conclusions MUG Lucifer prim, MUG Lucifer met and isolated and immortalized fibroblasts from the same patient represent an ideal in vitro model to explore the biology of CCS. 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author	Karner, Christina
spellingShingle	Karner, Christina misc Clear cell sarcoma misc Metastases misc Epigenetic hall marks misc Arginine methylation Targeting epigenetic features in clear cell sarcomas based on patient-derived cell lines
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topic_title	Targeting epigenetic features in clear cell sarcomas based on patient-derived cell lines Clear cell sarcoma (dpeaa)DE-He213 Metastases (dpeaa)DE-He213 Epigenetic hall marks (dpeaa)DE-He213 Arginine methylation (dpeaa)DE-He213
topic	misc Clear cell sarcoma misc Metastases misc Epigenetic hall marks misc Arginine methylation
topic_unstemmed	misc Clear cell sarcoma misc Metastases misc Epigenetic hall marks misc Arginine methylation
topic_browse	misc Clear cell sarcoma misc Metastases misc Epigenetic hall marks misc Arginine methylation
format_facet	Elektronische Aufsätze Aufsätze Elektronische Ressource
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title	Targeting epigenetic features in clear cell sarcomas based on patient-derived cell lines
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title_full	Targeting epigenetic features in clear cell sarcomas based on patient-derived cell lines
author_sort	Karner, Christina
journal	Journal of translational medicine
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author_browse	Karner, Christina Anders, Ines Vejzovic, Djenana Szkandera, Joanna Scheipl, Susanne Deutsch, Alexander J. A. Weiss, Larissa Vierlinger, Klemens Kolb, Dagmar Kühberger, Stefan Heitzer, Ellen Habisch, Hansjörg Zhang, Fangrong Madl, Tobias Reininger-Gutmann, Birgit Liegl-Atzwanger, Bernadette Rinner, Beate
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format_se	Elektronische Aufsätze
author-letter	Karner, Christina
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title_sort	targeting epigenetic features in clear cell sarcomas based on patient-derived cell lines
title_auth	Targeting epigenetic features in clear cell sarcomas based on patient-derived cell lines
abstract	Background Clear cell sarcomas (CCSs) are translocated aggressive malignancies, most commonly affecting young adults with a high incidence of metastases and a poor prognosis. Research into the disease is more feasible when adequate models are available. By establishing CCS cell lines from a primary and metastatic lesion and isolating healthy fibroblasts from the same patient, the in vivo process is accurately reflected and aspects of clinical multistep carcinogenesis recapitulated. Methods Isolated tumor cells and normal healthy skin fibroblasts from the same patient were compared in terms of growth behavior and morphological characteristics using light and electron microscopy. Tumorigenicity potential was determined by soft agar colony formation assay and in vivo xenograft applications. While genetic differences between the two lineages were examined by copy number alternation profiles, nuclear magnetic resonance spectroscopy determined arginine methylation as epigenetic features. Potential anti-tumor effects of a protein arginine n-methyltransferase type I (PRMT1) inhibitor were elicited in 2D and 3D cell culture experiments using cell viability and apoptosis assays. Statistical significance was calculated by one-way ANOVA and unpaired t-test. Results The two established CCS cell lines named MUG Lucifer prim and MUG Lucifer met showed differences in morphology, genetic and epigenetic data, reflecting the respective original tissue. The detailed cell line characterization especially in regards to the epigenetic domain allows investigation of new innovative therapies. Based on the epigenetic data, a PRMT1 inhibitor was used to demonstrate the targeted antitumor effect; normal tissue cells isolated and immortalized from the same patient were not affected with the $ IC_{50} $ used. Conclusions MUG Lucifer prim, MUG Lucifer met and isolated and immortalized fibroblasts from the same patient represent an ideal in vitro model to explore the biology of CCS. Based on this cell culture model, novel therapies could be tested in the form of PRMT1 inhibitors, which drive tumor cells into apoptosis, but show no effect on fibroblasts, further supporting their potential as promising treatment options in the combat against CCS. The data substantiate the importance of tailored therapies in the advanced metastatic stage of CCS. © The Author(s) 2023
abstractGer	Background Clear cell sarcomas (CCSs) are translocated aggressive malignancies, most commonly affecting young adults with a high incidence of metastases and a poor prognosis. Research into the disease is more feasible when adequate models are available. By establishing CCS cell lines from a primary and metastatic lesion and isolating healthy fibroblasts from the same patient, the in vivo process is accurately reflected and aspects of clinical multistep carcinogenesis recapitulated. Methods Isolated tumor cells and normal healthy skin fibroblasts from the same patient were compared in terms of growth behavior and morphological characteristics using light and electron microscopy. Tumorigenicity potential was determined by soft agar colony formation assay and in vivo xenograft applications. While genetic differences between the two lineages were examined by copy number alternation profiles, nuclear magnetic resonance spectroscopy determined arginine methylation as epigenetic features. Potential anti-tumor effects of a protein arginine n-methyltransferase type I (PRMT1) inhibitor were elicited in 2D and 3D cell culture experiments using cell viability and apoptosis assays. Statistical significance was calculated by one-way ANOVA and unpaired t-test. Results The two established CCS cell lines named MUG Lucifer prim and MUG Lucifer met showed differences in morphology, genetic and epigenetic data, reflecting the respective original tissue. The detailed cell line characterization especially in regards to the epigenetic domain allows investigation of new innovative therapies. Based on the epigenetic data, a PRMT1 inhibitor was used to demonstrate the targeted antitumor effect; normal tissue cells isolated and immortalized from the same patient were not affected with the $ IC_{50} $ used. Conclusions MUG Lucifer prim, MUG Lucifer met and isolated and immortalized fibroblasts from the same patient represent an ideal in vitro model to explore the biology of CCS. Based on this cell culture model, novel therapies could be tested in the form of PRMT1 inhibitors, which drive tumor cells into apoptosis, but show no effect on fibroblasts, further supporting their potential as promising treatment options in the combat against CCS. The data substantiate the importance of tailored therapies in the advanced metastatic stage of CCS. © The Author(s) 2023
abstract_unstemmed	Background Clear cell sarcomas (CCSs) are translocated aggressive malignancies, most commonly affecting young adults with a high incidence of metastases and a poor prognosis. Research into the disease is more feasible when adequate models are available. By establishing CCS cell lines from a primary and metastatic lesion and isolating healthy fibroblasts from the same patient, the in vivo process is accurately reflected and aspects of clinical multistep carcinogenesis recapitulated. Methods Isolated tumor cells and normal healthy skin fibroblasts from the same patient were compared in terms of growth behavior and morphological characteristics using light and electron microscopy. Tumorigenicity potential was determined by soft agar colony formation assay and in vivo xenograft applications. While genetic differences between the two lineages were examined by copy number alternation profiles, nuclear magnetic resonance spectroscopy determined arginine methylation as epigenetic features. Potential anti-tumor effects of a protein arginine n-methyltransferase type I (PRMT1) inhibitor were elicited in 2D and 3D cell culture experiments using cell viability and apoptosis assays. Statistical significance was calculated by one-way ANOVA and unpaired t-test. Results The two established CCS cell lines named MUG Lucifer prim and MUG Lucifer met showed differences in morphology, genetic and epigenetic data, reflecting the respective original tissue. The detailed cell line characterization especially in regards to the epigenetic domain allows investigation of new innovative therapies. Based on the epigenetic data, a PRMT1 inhibitor was used to demonstrate the targeted antitumor effect; normal tissue cells isolated and immortalized from the same patient were not affected with the $ IC_{50} $ used. Conclusions MUG Lucifer prim, MUG Lucifer met and isolated and immortalized fibroblasts from the same patient represent an ideal in vitro model to explore the biology of CCS. Based on this cell culture model, novel therapies could be tested in the form of PRMT1 inhibitors, which drive tumor cells into apoptosis, but show no effect on fibroblasts, further supporting their potential as promising treatment options in the combat against CCS. The data substantiate the importance of tailored therapies in the advanced metastatic stage of CCS. © The Author(s) 2023
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title_short	Targeting epigenetic features in clear cell sarcomas based on patient-derived cell lines
url	https://dx.doi.org/10.1186/s12967-022-03843-4
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author2	Anders, Ines Vejzovic, Djenana Szkandera, Joanna Scheipl, Susanne Deutsch, Alexander J. A. Weiss, Larissa Vierlinger, Klemens Kolb, Dagmar Kühberger, Stefan Heitzer, Ellen Habisch, Hansjörg Zhang, Fangrong Madl, Tobias Reininger-Gutmann, Birgit Liegl-Atzwanger, Bernadette Rinner, Beate
author2Str	Anders, Ines Vejzovic, Djenana Szkandera, Joanna Scheipl, Susanne Deutsch, Alexander J. A. Weiss, Larissa Vierlinger, Klemens Kolb, Dagmar Kühberger, Stefan Heitzer, Ellen Habisch, Hansjörg Zhang, Fangrong Madl, Tobias Reininger-Gutmann, Birgit Liegl-Atzwanger, Bernadette Rinner, Beate
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Targeting epigenetic features in clear cell sarcomas based on patient-derived cell lines

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