A New Patient-Derived Metastatic Glioblastoma Cell Line: Characterisation and Response to Sodium Selenite Anticancer Agent
Glioblastoma multiform (GBM) tumors are very heterogeneous, organized in a hierarchical pattern, including cancer stem cells (CSC), and are responsible for development, maintenance, and cancer relapse. Therefore, it is relevant to establish new GBM cell lines with CSC characteristics to develop new...
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| Format: | Article |
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MDPI AG
2018-12-01
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| Series: | Cancers |
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| Online Access: | http://www.mdpi.com/2072-6694/11/1/12 |
| _version_ | 1797713207848075264 |
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| author | Sylvie Berthier Louis Larrouquère Pierre Champelovier Edwige Col Christine Lefebvre Cécile Cottet-Rouselle Josiane Arnaud Catherine Garrel François Laporte Jean Boutonnat Patrice Faure Florence Hazane-Puch |
| author_facet | Sylvie Berthier Louis Larrouquère Pierre Champelovier Edwige Col Christine Lefebvre Cécile Cottet-Rouselle Josiane Arnaud Catherine Garrel François Laporte Jean Boutonnat Patrice Faure Florence Hazane-Puch |
| author_sort | Sylvie Berthier |
| collection | DOAJ |
| description | Glioblastoma multiform (GBM) tumors are very heterogeneous, organized in a hierarchical pattern, including cancer stem cells (CSC), and are responsible for development, maintenance, and cancer relapse. Therefore, it is relevant to establish new GBM cell lines with CSC characteristics to develop new treatments. A new human GBM cell line, named R2J, was established from the cerebro-spinal fluid (CSF) of a patient affected by GBM with leptomeningeal metastasis. R2J cells exhibits an abnormal karyotype and form self-renewable spheres in a serum-free medium. Original tumor, R2J, cultured in monolayer (2D) and in spheres showed a persistence expression of CD44, CD56 (except in monolayer), EGFR, Ki67, Nestin, and vimentin. The R2J cell line is tumorigenic and possesses CSC properties. We tested in vitro the anticancer effects of sodium selenite (SS) compared to temozolomide TMZ. SS was absorbed by R2J cells, was cytotoxic, induced an oxidative stress, and arrested cell growth in G2M before inducing both necrosis and apoptosis via caspase-3. SS also modified dimethyl-histone-3-lysine-9 (H3K9m2) levels and decreased histone deacetylase (HDAC) activity, suggesting anti-invasiveness potential. This study highlights the value of this new GBM cell line for preclinical modeling of clinically relevant, patient specific GBM and opens a therapeutic window to test SS to target resistant and recurrent GBM. |
| first_indexed | 2024-03-12T07:33:01Z |
| format | Article |
| id | doaj.art-373fe01e0c7f4d83a74c623ac94d9264 |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-12T07:33:01Z |
| publishDate | 2018-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-373fe01e0c7f4d83a74c623ac94d92642023-09-02T21:37:42ZengMDPI AGCancers2072-66942018-12-011111210.3390/cancers11010012cancers11010012A New Patient-Derived Metastatic Glioblastoma Cell Line: Characterisation and Response to Sodium Selenite Anticancer AgentSylvie Berthier0Louis Larrouquère1Pierre Champelovier2Edwige Col3Christine Lefebvre4Cécile Cottet-Rouselle5Josiane Arnaud6Catherine Garrel7François Laporte8Jean Boutonnat9Patrice Faure10Florence Hazane-Puch11Cytometry Platform, Institute of Biology and Pathology, Grenoble Alpes Hospital, CS10217, Grenoble CEDEX 9, FranceBrainTech Lab, INSERM U1205, 38000 Grenoble, FranceCytometry Platform, Institute of Biology and Pathology, Grenoble Alpes Hospital, CS10217, Grenoble CEDEX 9, FranceUnit of Anatomopathology, Institute of Biology and Pathology, Grenoble Alpes Hospital, CS10217, Grenoble CEDEX 9, FranceLaboratory of Hematology, Onco-Genetic and Immunology, Institute of Biology and Pathology, Grenoble Alpes Hospital, CS10217, Grenoble CEDEX 9, FranceLaboratory of Fundamental and Applied Bioenergetics (LBFA) and SFR BEeSy, University Grenoble Alpes, Inserm U1055, 38000 Grenoble, FranceLaboratory of Fundamental and Applied Bioenergetics (LBFA) and SFR BEeSy, University Grenoble Alpes, Inserm U1055, 38000 Grenoble, FranceUnit Nutritional and Hormonal Biochemistry, Institute of Biology and Pathology, Grenoble Alpes Hospital, CS10217, 38043 Grenoble CEDEX 9, FranceUnit Nutritional and Hormonal Biochemistry, Institute of Biology and Pathology, Grenoble Alpes Hospital, CS10217, 38043 Grenoble CEDEX 9, FranceUnit of Anatomopathology, Institute of Biology and Pathology, Grenoble Alpes Hospital, CS10217, Grenoble CEDEX 9, FranceUnit Nutritional and Hormonal Biochemistry, Institute of Biology and Pathology, Grenoble Alpes Hospital, CS10217, 38043 Grenoble CEDEX 9, FranceUnit Nutritional and Hormonal Biochemistry, Institute of Biology and Pathology, Grenoble Alpes Hospital, CS10217, 38043 Grenoble CEDEX 9, FranceGlioblastoma multiform (GBM) tumors are very heterogeneous, organized in a hierarchical pattern, including cancer stem cells (CSC), and are responsible for development, maintenance, and cancer relapse. Therefore, it is relevant to establish new GBM cell lines with CSC characteristics to develop new treatments. A new human GBM cell line, named R2J, was established from the cerebro-spinal fluid (CSF) of a patient affected by GBM with leptomeningeal metastasis. R2J cells exhibits an abnormal karyotype and form self-renewable spheres in a serum-free medium. Original tumor, R2J, cultured in monolayer (2D) and in spheres showed a persistence expression of CD44, CD56 (except in monolayer), EGFR, Ki67, Nestin, and vimentin. The R2J cell line is tumorigenic and possesses CSC properties. We tested in vitro the anticancer effects of sodium selenite (SS) compared to temozolomide TMZ. SS was absorbed by R2J cells, was cytotoxic, induced an oxidative stress, and arrested cell growth in G2M before inducing both necrosis and apoptosis via caspase-3. SS also modified dimethyl-histone-3-lysine-9 (H3K9m2) levels and decreased histone deacetylase (HDAC) activity, suggesting anti-invasiveness potential. This study highlights the value of this new GBM cell line for preclinical modeling of clinically relevant, patient specific GBM and opens a therapeutic window to test SS to target resistant and recurrent GBM.http://www.mdpi.com/2072-6694/11/1/12Glioblastomacancer stem cellsnew cell linesodium selenitexenograftcell deathepigenetics |
| spellingShingle | Sylvie Berthier Louis Larrouquère Pierre Champelovier Edwige Col Christine Lefebvre Cécile Cottet-Rouselle Josiane Arnaud Catherine Garrel François Laporte Jean Boutonnat Patrice Faure Florence Hazane-Puch A New Patient-Derived Metastatic Glioblastoma Cell Line: Characterisation and Response to Sodium Selenite Anticancer Agent Cancers Glioblastoma cancer stem cells new cell line sodium selenite xenograft cell death epigenetics |
| title | A New Patient-Derived Metastatic Glioblastoma Cell Line: Characterisation and Response to Sodium Selenite Anticancer Agent |
| title_full | A New Patient-Derived Metastatic Glioblastoma Cell Line: Characterisation and Response to Sodium Selenite Anticancer Agent |
| title_fullStr | A New Patient-Derived Metastatic Glioblastoma Cell Line: Characterisation and Response to Sodium Selenite Anticancer Agent |
| title_full_unstemmed | A New Patient-Derived Metastatic Glioblastoma Cell Line: Characterisation and Response to Sodium Selenite Anticancer Agent |
| title_short | A New Patient-Derived Metastatic Glioblastoma Cell Line: Characterisation and Response to Sodium Selenite Anticancer Agent |
| title_sort | new patient derived metastatic glioblastoma cell line characterisation and response to sodium selenite anticancer agent |
| topic | Glioblastoma cancer stem cells new cell line sodium selenite xenograft cell death epigenetics |
| url | http://www.mdpi.com/2072-6694/11/1/12 |
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