Pagani Francesca, Gryzik Magdalena, Somenza Elena, Cominelli Manuela, Balzarini Piera, Schreiber Alberto, Mattavelli Davide, Nicolai Piero, Doglietto Francesco, Poliani Pietro Luigi
Pathology Unit, Department of Molecular and Translational Medicine, University of Brescia, 25123 Brescia, Italy.
Unit 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, Italy.
J Pers Med. 2023 Feb 27;13(3):425. doi: 10.3390/jpm13030425.
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 duplication and 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 -deleted chordoma cell lines are exceedingly rare. Hereby, we established and characterized a novel human -deleted chordoma cell line (CH3) from a primary skull base chordoma. Cells exhibited morphological and molecular features of the parent tumour, including 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 -deleted chordomas.
脊索瘤是一种罕见的起源于脊索的原发性恶性肿瘤，通常沿中轴骨骼发生，尤其好发于颅底和骶尾区域。尽管脊索瘤通常生长缓慢，但根据其侵袭行为以及不同的组织学类型和分子改变（包括基因重复和纯合缺失），它也可能具有侵袭性。此外，还观察到了部分或完全的PTEN缺失。PTEN是Akt/mTOR通路的负调节因子，在缺乏PTEN表达的细胞中，Akt/mTOR的过度激活会促进细胞增殖和侵袭。mTOR抑制剂作用于该通路，脊索瘤细胞的体外模型将有助于进一步研究这一问题。然而，脊索瘤细胞系的分离和培养具有挑战性，且缺失型脊索瘤细胞系极为罕见。在此，我们从一例原发性颅底脊索瘤中建立并鉴定了一种新型的人缺失型脊索瘤细胞系（CH3）。该细胞表现出亲本肿瘤的形态和分子特征，包括Brachyury和EMA的缺失与表达。此外，我们研究了mTOR通路的激活情况以及细胞对mTOR抑制剂的反应。CH3细胞对雷帕霉素治疗敏感，这表明mTOR抑制剂可能是缺失型脊索瘤患者的一个有价值的治疗选择。
