Phenotypical Flexibility of the EGFRvIII-Positive Glioblastoma Cell Line and the Multidirectional Influence of TGFβ and EGF on These Cells—EGFRvIII Appears as a Weak Oncogene
Background: The biological role of EGFRvIII (epidermal growth factor receptor variant three) remains unclear. Methods: Three glioblastoma DK-MG sublines were tested with EGF (epidermal growth factor) and TGFβ (transforming growth factor β). Sublines were characterized by an increased percentage of E...
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MDPI AG
2022-10-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/23/20/12129 |
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| author | Aneta Włodarczyk Cezary Tręda Adrianna Rutkowska Dagmara Grot Weronika Dobrewa Amelia Kierasińska Marta Węgierska Tomasz Wasiak Tadeusz Strózik Piotr Rieske Ewelina Stoczyńska-Fidelus |
| author_facet | Aneta Włodarczyk Cezary Tręda Adrianna Rutkowska Dagmara Grot Weronika Dobrewa Amelia Kierasińska Marta Węgierska Tomasz Wasiak Tadeusz Strózik Piotr Rieske Ewelina Stoczyńska-Fidelus |
| author_sort | Aneta Włodarczyk |
| collection | DOAJ |
| description | Background: The biological role of EGFRvIII (epidermal growth factor receptor variant three) remains unclear. Methods: Three glioblastoma DK-MG sublines were tested with EGF (epidermal growth factor) and TGFβ (transforming growth factor β). Sublines were characterized by an increased percentage of EGFRvIII-positive cells and doubling time (DK-MG<sup>low</sup> to DK-MG<sup>extra-high</sup>), number of amplicons, and EGFRvIII mRNA expression. The influence of the growth factors on primary EGFRvIII positive glioblastomas was assessed. Results: The overexpression of exoEGFRvIII in DK-MG<sup>high</sup> did not convert them into DK-MG<sup>extra-high</sup>, and this overexpression did not change DK-MG<sup>low</sup> to DK-MG<sup>high</sup>; however, the overexpression of RAS<sup>G12V</sup> increased the proliferation of DK-MG<sup>low</sup>. Moreover, the highest EGFRvIII phosphorylation in DK-MG<sup>extra-high</sup> did not cause relevant AKT (known as protein kinase B) and ERK (extracellular signal-regulated kinase) activation. Further analyses indicate that TGFβ is able to induce apoptosis of DK-MG<sup>high</sup> cells. This subline was able to convert to DK-MG<sup>extra-high</sup>, which appeared resistant to this proapoptotic effect. EGF acted as a pro-survival factor and stimulated proliferation; however, simultaneous senescence induction in DK-MG<sup>extra-high</sup> cells was ambiguous. Primary EGFRvIII positive (and SOX2 (SRY-Box Transcription Factor 2) positive or SOX2 negative) glioblastoma cells differentially responded to EGF and TGFβ. Conclusions: The roles of TGFβ and EGF in the EGFRvIII context remain unclear. EGFRvIII appears as a weak oncogene and not a marker of GSC (glioma stem cells). Hence, it may not be a proper target for CAR-T (chimeric antigen receptor T cells). |
| first_indexed | 2024-03-09T12:15:46Z |
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| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T12:15:46Z |
| publishDate | 2022-10-01 |
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| series | International Journal of Molecular Sciences |
| spelling | doaj.art-5bc09db68d2a462a84df9fb318db9aa22023-11-30T22:46:26ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-10-0123201212910.3390/ijms232012129Phenotypical Flexibility of the EGFRvIII-Positive Glioblastoma Cell Line and the Multidirectional Influence of TGFβ and EGF on These Cells—EGFRvIII Appears as a Weak OncogeneAneta Włodarczyk0Cezary Tręda1Adrianna Rutkowska2Dagmara Grot3Weronika Dobrewa4Amelia Kierasińska5Marta Węgierska6Tomasz Wasiak7Tadeusz Strózik8Piotr Rieske9Ewelina Stoczyńska-Fidelus10Department of Tumor Biology, Medical University of Lodz, Zeligowskiego 7/9 St., 90-752 Lodz, PolandDepartment of Tumor Biology, Medical University of Lodz, Zeligowskiego 7/9 St., 90-752 Lodz, PolandDepartment of Tumor Biology, Medical University of Lodz, Zeligowskiego 7/9 St., 90-752 Lodz, PolandDepartment of Tumor Biology, Medical University of Lodz, Zeligowskiego 7/9 St., 90-752 Lodz, PolandDepartment of Tumor Biology, Medical University of Lodz, Zeligowskiego 7/9 St., 90-752 Lodz, PolandDepartment of Tumor Biology, Medical University of Lodz, Zeligowskiego 7/9 St., 90-752 Lodz, PolandDepartment of Tumor Biology, Medical University of Lodz, Zeligowskiego 7/9 St., 90-752 Lodz, PolandDepartment of Molecular Biology, Medical University of Lodz, Zeligowskiego 7/9 St., 90-752 Lodz, PolandDepartment of Molecular Biology, Medical University of Lodz, Zeligowskiego 7/9 St., 90-752 Lodz, PolandDepartment of Tumor Biology, Medical University of Lodz, Zeligowskiego 7/9 St., 90-752 Lodz, PolandDepartment of Tumor Biology, Medical University of Lodz, Zeligowskiego 7/9 St., 90-752 Lodz, PolandBackground: The biological role of EGFRvIII (epidermal growth factor receptor variant three) remains unclear. Methods: Three glioblastoma DK-MG sublines were tested with EGF (epidermal growth factor) and TGFβ (transforming growth factor β). Sublines were characterized by an increased percentage of EGFRvIII-positive cells and doubling time (DK-MG<sup>low</sup> to DK-MG<sup>extra-high</sup>), number of amplicons, and EGFRvIII mRNA expression. The influence of the growth factors on primary EGFRvIII positive glioblastomas was assessed. Results: The overexpression of exoEGFRvIII in DK-MG<sup>high</sup> did not convert them into DK-MG<sup>extra-high</sup>, and this overexpression did not change DK-MG<sup>low</sup> to DK-MG<sup>high</sup>; however, the overexpression of RAS<sup>G12V</sup> increased the proliferation of DK-MG<sup>low</sup>. Moreover, the highest EGFRvIII phosphorylation in DK-MG<sup>extra-high</sup> did not cause relevant AKT (known as protein kinase B) and ERK (extracellular signal-regulated kinase) activation. Further analyses indicate that TGFβ is able to induce apoptosis of DK-MG<sup>high</sup> cells. This subline was able to convert to DK-MG<sup>extra-high</sup>, which appeared resistant to this proapoptotic effect. EGF acted as a pro-survival factor and stimulated proliferation; however, simultaneous senescence induction in DK-MG<sup>extra-high</sup> cells was ambiguous. Primary EGFRvIII positive (and SOX2 (SRY-Box Transcription Factor 2) positive or SOX2 negative) glioblastoma cells differentially responded to EGF and TGFβ. Conclusions: The roles of TGFβ and EGF in the EGFRvIII context remain unclear. EGFRvIII appears as a weak oncogene and not a marker of GSC (glioma stem cells). Hence, it may not be a proper target for CAR-T (chimeric antigen receptor T cells).https://www.mdpi.com/1422-0067/23/20/12129apoptosisEGFRvIIIEMT-like phenomenonGBTGFβsenescence |
| spellingShingle | Aneta Włodarczyk Cezary Tręda Adrianna Rutkowska Dagmara Grot Weronika Dobrewa Amelia Kierasińska Marta Węgierska Tomasz Wasiak Tadeusz Strózik Piotr Rieske Ewelina Stoczyńska-Fidelus Phenotypical Flexibility of the EGFRvIII-Positive Glioblastoma Cell Line and the Multidirectional Influence of TGFβ and EGF on These Cells—EGFRvIII Appears as a Weak Oncogene International Journal of Molecular Sciences apoptosis EGFRvIII EMT-like phenomenon GB TGFβ senescence |
| title | Phenotypical Flexibility of the EGFRvIII-Positive Glioblastoma Cell Line and the Multidirectional Influence of TGFβ and EGF on These Cells—EGFRvIII Appears as a Weak Oncogene |
| title_full | Phenotypical Flexibility of the EGFRvIII-Positive Glioblastoma Cell Line and the Multidirectional Influence of TGFβ and EGF on These Cells—EGFRvIII Appears as a Weak Oncogene |
| title_fullStr | Phenotypical Flexibility of the EGFRvIII-Positive Glioblastoma Cell Line and the Multidirectional Influence of TGFβ and EGF on These Cells—EGFRvIII Appears as a Weak Oncogene |
| title_full_unstemmed | Phenotypical Flexibility of the EGFRvIII-Positive Glioblastoma Cell Line and the Multidirectional Influence of TGFβ and EGF on These Cells—EGFRvIII Appears as a Weak Oncogene |
| title_short | Phenotypical Flexibility of the EGFRvIII-Positive Glioblastoma Cell Line and the Multidirectional Influence of TGFβ and EGF on These Cells—EGFRvIII Appears as a Weak Oncogene |
| title_sort | phenotypical flexibility of the egfrviii positive glioblastoma cell line and the multidirectional influence of tgfβ and egf on these cells egfrviii appears as a weak oncogene |
| topic | apoptosis EGFRvIII EMT-like phenomenon GB TGFβ senescence |
| url | https://www.mdpi.com/1422-0067/23/20/12129 |
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