Targeting mTOR Pathway in PTEN Deleted Newly Isolated Chordoma Cell Line
Chordomas are rare primary malignant tumours of notochordal origin usually arising along the axial skeleton with particular predilection of the skull base and sacrococcygeal region. Albeit usually slow-growing, chordomas can be aggressive mostly depending on their invasive behaviour and according to...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-02-01
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| Series: | Journal of Personalized Medicine |
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| Online Access: | https://www.mdpi.com/2075-4426/13/3/425 |
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| author | Francesca Pagani Magdalena Gryzik Elena Somenza Manuela Cominelli Piera Balzarini Alberto Schreiber Davide Mattavelli Piero Nicolai Francesco Doglietto Pietro Luigi Poliani |
| author_facet | Francesca Pagani Magdalena Gryzik Elena Somenza Manuela Cominelli Piera Balzarini Alberto Schreiber Davide Mattavelli Piero Nicolai Francesco Doglietto Pietro Luigi Poliani |
| author_sort | Francesca Pagani |
| collection | DOAJ |
| description | Chordomas are rare primary malignant tumours of notochordal origin usually arising along the axial skeleton with particular predilection of the skull base and sacrococcygeal region. Albeit usually slow-growing, chordomas can be aggressive mostly depending on their invasive behaviour and according to different histotypes and molecular alterations, including <i>TBXT</i> duplication and <i>SMARCB1</i> homozygous deletion. Partial or complete PTEN deficiency has also been observed. PTEN is a negative regulator of the Akt/mTOR pathway and hyperactivation of Akt/mTOR in cells lacking PTEN expression contributes to cell proliferation and invasiveness. This pathway is targeted by mTOR inhibitors and the availability of in vitro models of chordoma cells will aid in further investigating this issue. However, isolation and maintenance of chordoma cell lines are challenging and <i>PTEN</i>-deleted chordoma cell lines are exceedingly rare. Hereby, we established and characterized a novel human <i>PTEN</i>-deleted chordoma cell line (CH3) from a primary skull base chordoma. Cells exhibited morphological and molecular features of the parent tumour, including <i>PTEN</i> loss and expression of Brachyury and EMA. Moreover, we investigated the activation of the mTOR pathway and cell response to mTOR inhibitors. CH3 cells were sensitive to Rapamycin treatment suggesting that mTOR inhibitors may represent a valuable option for patients suffering from <i>PTEN</i>-deleted chordomas. |
| first_indexed | 2024-03-11T06:19:20Z |
| format | Article |
| id | doaj.art-8fd7b48cf65b45e7bf14bc72f1779975 |
| institution | Directory Open Access Journal |
| issn | 2075-4426 |
| language | English |
| last_indexed | 2024-03-11T06:19:20Z |
| publishDate | 2023-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Journal of Personalized Medicine |
| spelling | doaj.art-8fd7b48cf65b45e7bf14bc72f17799752023-11-17T12:02:10ZengMDPI AGJournal of Personalized Medicine2075-44262023-02-0113342510.3390/jpm13030425Targeting mTOR Pathway in PTEN Deleted Newly Isolated Chordoma Cell LineFrancesca Pagani0Magdalena Gryzik1Elena Somenza2Manuela Cominelli3Piera Balzarini4Alberto Schreiber5Davide Mattavelli6Piero Nicolai7Francesco Doglietto8Pietro Luigi Poliani9Pathology Unit, Department of Molecular and Translational Medicine, University of Brescia, 25123 Brescia, ItalyPathology Unit, Department of Molecular and Translational Medicine, University of Brescia, 25123 Brescia, ItalyPathology Unit, Department of Molecular and Translational Medicine, University of Brescia, 25123 Brescia, ItalyPathology Unit, Department of Molecular and Translational Medicine, University of Brescia, 25123 Brescia, ItalyPathology Unit, Department of Molecular and Translational Medicine, University of Brescia, 25123 Brescia, ItalyUnit of Otorhinolaryngology-Head and Neck Surgery, ASST Spedali Civili Brescia, Department of Medical and Surgical Specialties, Radiological Sciences, and Public Health, University of Brescia, 25123 Brescia, ItalyUnit of Otorhinolaryngology-Head and Neck Surgery, ASST Spedali Civili Brescia, Department of Medical and Surgical Specialties, Radiological Sciences, and Public Health, University of Brescia, 25123 Brescia, ItalySection of Otorhinolaryngology-Head and Neck Surgery, Department of Neurosciences, University of Padova—Azienda Ospedale-Università di Padova, 35128 Padova, ItalyFondazione Policlinico Universitario Agostino Gemelli IRCCS, Catholic University School of Medicine, 00168 Rome, ItalyPathology Unit, Department of Molecular and Translational Medicine, University of Brescia, 25123 Brescia, ItalyChordomas are rare primary malignant tumours of notochordal origin usually arising along the axial skeleton with particular predilection of the skull base and sacrococcygeal region. Albeit usually slow-growing, chordomas can be aggressive mostly depending on their invasive behaviour and according to different histotypes and molecular alterations, including <i>TBXT</i> duplication and <i>SMARCB1</i> homozygous deletion. Partial or complete PTEN deficiency has also been observed. PTEN is a negative regulator of the Akt/mTOR pathway and hyperactivation of Akt/mTOR in cells lacking PTEN expression contributes to cell proliferation and invasiveness. This pathway is targeted by mTOR inhibitors and the availability of in vitro models of chordoma cells will aid in further investigating this issue. However, isolation and maintenance of chordoma cell lines are challenging and <i>PTEN</i>-deleted chordoma cell lines are exceedingly rare. Hereby, we established and characterized a novel human <i>PTEN</i>-deleted chordoma cell line (CH3) from a primary skull base chordoma. Cells exhibited morphological and molecular features of the parent tumour, including <i>PTEN</i> loss and expression of Brachyury and EMA. Moreover, we investigated the activation of the mTOR pathway and cell response to mTOR inhibitors. CH3 cells were sensitive to Rapamycin treatment suggesting that mTOR inhibitors may represent a valuable option for patients suffering from <i>PTEN</i>-deleted chordomas.https://www.mdpi.com/2075-4426/13/3/425chordomaCH3 cell linemTORrapamycin |
| spellingShingle | Francesca Pagani Magdalena Gryzik Elena Somenza Manuela Cominelli Piera Balzarini Alberto Schreiber Davide Mattavelli Piero Nicolai Francesco Doglietto Pietro Luigi Poliani Targeting mTOR Pathway in PTEN Deleted Newly Isolated Chordoma Cell Line Journal of Personalized Medicine chordoma CH3 cell line mTOR rapamycin |
| title | Targeting mTOR Pathway in PTEN Deleted Newly Isolated Chordoma Cell Line |
| title_full | Targeting mTOR Pathway in PTEN Deleted Newly Isolated Chordoma Cell Line |
| title_fullStr | Targeting mTOR Pathway in PTEN Deleted Newly Isolated Chordoma Cell Line |
| title_full_unstemmed | Targeting mTOR Pathway in PTEN Deleted Newly Isolated Chordoma Cell Line |
| title_short | Targeting mTOR Pathway in PTEN Deleted Newly Isolated Chordoma Cell Line |
| title_sort | targeting mtor pathway in pten deleted newly isolated chordoma cell line |
| topic | chordoma CH3 cell line mTOR rapamycin |
| url | https://www.mdpi.com/2075-4426/13/3/425 |
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