Establishment and characterization of a novel cell line derived from human thymoma AB tumor

Gökmen–Polar, Yesim; Sanders, Kerry L.; Goswami, Chirayu; Cano, Oscar D.; Zaheer, Narjis A.; Jain, Rohit; Kesler, Kenneth A.; Nelson, Robert P.; Vance, Gail H.; Smith, Drew; Li, Lang; Cardoso, Angelo A.; Badve, Sunil; Loehrer, Patrick J.; Sledge, George W.

doi:10.1038/labinvest.2012.115

Cited by 26 publications

(24 citation statements)

References 36 publications

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“…A so far unresolved key problem that has strongly inhibited functional in vitro and preclinical in vivo studies is the paucity of permanent bona fide thymoma and thymic carcinoma cell lines 27, 89, 90 and the virtual absence of relevant spontaneous and xenograft-based animal models. 91 Except for the rarity of thymomas and thymic carcinomas, the lack of cell lines and functional xenografts is likely due to the essential need of neoplastic thymic epithelial cells for crosstalk with stromal cells and particularly developing T cells in the case of thymomas to prevent senescence in vitro.…”

Section: Perspectives and Challengesmentioning

confidence: 99%

The 2015 World Health Organization Classification of Tumors of the Thymus: Continuity and Changes

Marx

Chan

Coindre

et al. 2015

Journal of Thoracic Oncology

519

420

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This overview of the 4th edition of the WHO Classification of thymic tumors has two aims. First, to comprehensively list the established and new tumour entities and variants that are described in the new WHO Classification of thymic epithelial tumors, germ cell tumors, lymphomas, dendritic cell and myeloid neoplasms, and soft tissue tumors of the thymus and mediastinum; second, to highlight major differences in the new WHO Classification that result from the progress that has been made since the 3rd edition in 2004 at immunohistochemical, genetic and conceptual levels. Refined diagnostic criteria for type A, AB, B1–B3 thymomas and thymic squamous cell carcinoma are given and will hopefully improve the reproducibility of the classification and its clinical relevance. The clinical perspective of the classification has been strengthened by involving experts from radiology, thoracic surgery and oncology; by incorporating state-of-the-art PET/CT images; and by depicting prototypic cytological specimens. This makes the thymus section of the new WHO Classification of Tumours of the Lung, Pleura, Thymus and Heart a valuable tool for pathologists, cytologists and clinicians alike. The impact of the new WHO Classification on therapeutic decisions is exemplified in this overview for thymic epithelial tumors and mediastinal lymphomas, and future perspectives and challenges are discussed.

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Section: Perspectives and Challengesmentioning

confidence: 99%

The 2015 World Health Organization Classification of Tumors of the Thymus: Continuity and Changes

Marx

Chan

Coindre

et al. 2015

Journal of Thoracic Oncology

519

420

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“…Taken together, these data were of significant therapeutic relevance: while pictilisib is mostly developed in breast cancers, which more frequently harbor PI3K alterations, phase II trials dedicated to thymic epithelial tumors were conducted with the IGF-1R inhibitor cixutumumab [33], the mTOR inhibitor everolimus [34] reporting on clinical antitumor activity in advanced, refractory cases. The IU-TAB-1-cell line was established from type AB thymoma, with phenotypic and molecular profiling but limited information of derivation protocol and success rate, and subsequent analysis of molecular pathways of interest [35].…”

Section: Discussionmentioning

confidence: 99%

Activation of the mTOR/ Akt pathway in thymic epithelial cells derived from thymomas

Maury

Vignaux

Drevet

et al. 2018

Preprint

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21The pathogenesis of thymic epithelial tumors remains poorly elucidated. The 22 PI3K/Akt/mTOR pathway plays a key role in various cancers; interestingly, several 23 phase I/II study reported a positive effect of mTOR inhibitors in disease control in 24 thymoma patients. A major limit for deciphering cellular and molecular events leading 25 to the transformation of thymic epithelial cells or for testing drug candidates is the lack 26 of reliable in vitro cell system 27 We analyzed protein expression and activation of key players of the Akt/mTOR 28 pathway namely Akt, mTOR, and P70S6K in thirteen A, B and AB thymomas as well 29 as in normal thymuses. While only Akt and the phospho-Akt were expressed in normal 30 thymuses, both Akt and mTOR were activated, with B2 thymomas expressing higher 31 level of activated phospho-Akt than A or AB subtypes. Phospho-P70S6K was 32 expressed in all thymic tumors whatever their subtypes, and absent in normal thymus. 33Interestingly, in primary thymic epithelial cells maintained for short period of time after 34 their derivation from seven AB and B thymomas, we report the activation of Akt; mTOR 35 and P70S6. Finally, we analyzed the effect of mTOR inhibitor on thymoma derived 36 epithelial cells and showed that rapamycin (100 nM/ ml) significantly reduced cell 37 proliferation. 38Our results suggest that the activation of the Akt/ mTOR pathway might participate to 39 the cell proliferation associated with tumor growth. Ultimately, our data enhance the 40 potential role of thymic epithelial cells derived from tissue specimens for in vitro 41 exploration of molecular abnormalities specific to rare thymic tumors. 43Thymic epithelial tumors (TETs) are rare epithelial malignancies (0.2-1.5%) of the 44 anterior mediastinum, with an estimated incidence about 1.3-3.2 cases worldwide [1]. 45The WHO classification distinguishes thymomas and thymic carcinomas [2]. 46 Thymomas are defined as A, AB, B1, B2, B3 sub-types according to the morphology 47 of tumor epithelial cells, the proportion of non-tumoral thymic lymphocytes (decreasing 48 from B1 to B3) that are associated with tumor cells, and their similarities to normal 49 thymic architecture. Thymic carcinomas present with a high degree of epithelial cells 50 atypia associated with a loss of normal thymic architecture. 51Surgical resection is the corner stone of the multimodal treatment of thymomas [3]. 52 Tumor stage [4] and radical complete surgical resection have been shown as 53 independent prognosis factor of best outcome [5-7]. Advanced or metastatic cases are 54 treated with induction chemotherapy, surgery, combined radiation-chemotherapy [8-55 11] with variable outcomes from 12 to 60% response [12-15]. 56 The pathogenesis of thymic epithelial tumors remains poorly elucidated. Sustained 57 efforts have been made to characterize molecular abnormalities occurring in TETs to 58 improve their treatment and eventually the patient prognosis. Sequencing of 197 59 cancer-related genes revealed the presence of non-synonymous so...

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“… 21 A novel thymoma cell line, named IU-TAB-1, was announced in 2012 as the latest thymoma cell line, established from a 53-year-old male patient with type AB thymoma. 22 …”

Section: Discussionmentioning

confidence: 99%

Establishment and characterization of a novel cell line derived from thymoma with myasthenia gravis patients

Wang

Zhang

et al. 2015

Thoracic Cancer

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BackgroundThymoma is a cancer with rare incidence, but it is a major malignancy in adult anterior mediastinum, occurring in about 40% of patients with myasthenia gravis. Because of the lack of thymic epithelial tumor cell lines, thymoma has lagged far behind other tumors in cytological studies. It is, therefore, quite necessary to establish a new thymic epithelial tumor cell line from Chinese patients to study the pathogenic mechanism and therapeutic methods.MethodsTwenty-three samples of tumor tissues were collected from thymoma and thymic carcinoma patients for primary culture by tissue explant, suspension cell culture method, and collagenase digestion. We detected the biological characteristics and origin of the cell line after the establishment of a novel thymoma cell line.ResultsA novel cell line, designed as Thy0517, was established from thymoma type AB with myasthenia gravis patients by tissue explant. As an immortalized cell line, it always has a stable growth cycle, and there is no change in characteristics and morphology after culturing for 18 months and passing 160 generations in vitro. The experimental data demonstrate that the cell line exhibits the growth characteristics of tumor cells, the doubling time of 37 hours, with tumorigenicity in vitro and chromosome abnormality. Immunocytochemistry indicated that the cell line positive expression of CK7, CK8/18, CK19, CK-pan, CD24, BCL-2, P63, Vimentin, epithelial membrane antigen and epidermal growth factor receptor, lymphocyte related antigen CD99, and TdT were negatively expressed.ConclusionsThe newly established thymic epithelial tumor cell line from Chinese patients provides a model in the study of thymoma and molecularly targeted therapies.

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Establishment and characterization of a novel cell line derived from human thymoma AB tumor

Cited by 26 publications

References 36 publications

The 2015 World Health Organization Classification of Tumors of the Thymus: Continuity and Changes

The 2015 World Health Organization Classification of Tumors of the Thymus: Continuity and Changes

Activation of the mTOR/ Akt pathway in thymic epithelial cells derived from thymomas

Establishment and characterization of a novel cell line derived from thymoma with myasthenia gravis patients

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