Establishment, Characterization and Comparison of Seven Authentic Anaplastic Thyroid Cancer Cell Lines Retaining Clinical Features of the Original Tumors

Onoda, Naoyoshi; Nakamura, Masanori; Aomatsu, Naoki; Noda, Shinichi; Kashiwagi, Shinichiro; Hirakawa, Kosei

doi:10.1007/s00268-013-2409-7

Cited by 19 publications

(23 citation statements)

References 40 publications

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“…Several cell lines harbor one of these gene mutations. By contrast, OCUT-2 is a unique cell line exhibiting alterations in both B-Raf and PI3KCA genes, resulting in completely aberrant proliferation signal generation independent of EGFR-mediated signaling (9). The results of our previous study may, thus, be interpreted as that the efficacy of EGFR-targeted therapy may be determined by the signaling status downstream of EGFR.…”

Section: Discussionmentioning

confidence: 71%

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Significant cytostatic effect of everolimus on a gefitinib-resistant anaplastic thyroid cancer cell line harboring PI3KCA gene mutation

Onoda

Nakamura

Aomatsu

et al. 2015

Molecular and Clinical Oncology

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Abstract. We previously demonstrated the efficacy of gefitinib, a tyrosine kinase inhibitor of the epidermal growth factor receptor (EGFR), on an anaplastic thyroid cancer (ATC) cell line. We also observed that gefitinib was not effective in regulating cell growth in a different ATC cell line that exhibited an altered EGFR-initiated signal transduction pathway. In the present study, we attempted to regulate the downstream effector of EGFR-Akt-mammalian target of rapamycin (mTOR) pathway by an mTOR inhibitor, everolimus. A total of 8 ATC cell lines were employed, 7 of which were established in our institute. OCUT-2 was known to carry a mutation in the phosphoinositide-3-kinase, catalytic, α polypeptide gene (PI3KCA) and to be gefitinib-resistant, whereas ACT-1 exhibited a remarkable growth arrest by gefitinib. All the cell lines were tested for the cytotoxic effect of everolimus. The mechanisms of cellular toxicity were investigated by EGFR stimulation, cell cycle and concurrent exposure to paclitaxel. In OCUT-2, but not in any of the other cell lines, everolimus achieved a significant growth inhibition (inhibition of 30 and 50% was achieved by concentrations of 0.8 and 5 nM, respectively). The growth in OCUT-2 was inhibited by everolimus, even with concordant EGFR stimulation. This effect was demonstrated by a G2M cell cycle arrest. An additive effect of everolimus onto the cytotoxic effect of paclitaxel was demonstrated at a dose of 1-2 nM. A significant growth inhibitory effect of everolimus on the gefitinib-resistant ATC cell line was demonstrated, suggesting a possible correlation between the efficacy of everolimus and PI3KCA gene mutation and the significance of molecular-targeted therapy in the management of ATC.

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Section: Discussionmentioning

confidence: 71%

“…OCUT-1-6 were established and characterized in our laboratory. A mutation of B-Raf V600E was found in OCUT-1-5 and a N-Ras mutation was found in the OCUT-6 and ACT-1 cell lines (9 MTT assay. The inhibitory effects of everolimus on the viability of these cell lines were measured by the MTT assay (7).…”

Section: Methodsmentioning

confidence: 99%

Significant cytostatic effect of everolimus on a gefitinib-resistant anaplastic thyroid cancer cell line harboring PI3KCA gene mutation

Onoda

Nakamura

Aomatsu

et al. 2015

Molecular and Clinical Oncology

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“…Thus, there is a need to develop and characterize novel cell lines that closely recapitulate thyroid cancer pathogenesis. In support of this, new thyroid cancer cell lines have recently been established, including cell lines derived from ATC, PTC, and FTC (15,24,41,42). Here, we report the generation of two new PTC-derived cell lines isolated from pleural effusions (CUTC5, CUTC48), one cell line derived from the primary tumor of a patient with ATC (CUTC60), and a fourth cell line derived from the primary tumor of a patient with metastatic FTC (CUTC61).…”

Section: Discussionmentioning

confidence: 92%

Establishment and Characterization of Four Novel Thyroid Cancer Cell Lines and PDX Models Expressing the RET/PTC1 Rearrangement, BRAFV600E, or RASQ61R as Drivers

Schweppe

Pozdeyev

Pike

et al. 2019

Molecular Cancer Research

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Cancer cell lines are critical models to study tumor progression and response to therapy. In 2008, we showed that approximately 50% of thyroid cancer cell lines were redundant or not of thyroid cancer origin. We therefore generated new authenticated thyroid cancer cell lines and patient-derived xenograft (PDX) models using in vitro and feeder cell approaches, and characterized these models in vitro and in vivo. We developed four thyroid cancer cell lines, two derived from 2 different patients with papillary thyroid cancer (PTC) pleural effusions, CUTC5, and CUTC48; one derived from a patient with anaplastic thyroid cancer (ATC), CUTC60; and one derived from a patient with follicular thyroid cancer (FTC), CUTC61. One PDX model (CUTC60-PDX) was also developed. Short tandem repeat (STR) genotyping showed that each cell line and PDX is unique and match the original patient tissue. The CUTC5 and CUTC60 cells harbor the BRAF (V600E) mutation, the CUTC48 cell line expresses the RET/PTC1 rearrangement, and the CUTC61 cells have the HRAS (Q61R) mutation. Moderate to high levels of PAX8 and variable levels of NKX2-1 were detected in each cell line and PDX. The CUTC5 and CUTC60 cell lines form tumors in orthotopic and flank xenograft mouse models. Implications:We have developed the second RET/PTC1expressing PTC-derived cell line in existence, which is a major advance in studying RET signaling. We have further linked all cell lines to the originating patients, providing a set of novel, authenticated thyroid cancer cell lines and PDX models to study advanced thyroid cancer.

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“…However, it has been shown that primary cell cultures better reflect the morphologic and genetic profile of the original tumor and predict response to therapies, compared to commercial cell lines [14][15][16]. Therefore, we used primary endometrioid EC cell cultures to determine the effect of metformin on tumor growth in vivo.…”

Section: Introductionmentioning

confidence: 98%

The antitumor effect of metformin with and without carboplatin on primary endometrioid endometrial carcinoma in vivo

Schrauwen

Coenegrachts

Cattaneo

et al. 2015

Gynecologic Oncology

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Establishment, Characterization and Comparison of Seven Authentic Anaplastic Thyroid Cancer Cell Lines Retaining Clinical Features of the Original Tumors

Abstract: Basic studies using authentic ATC cell lines retaining the clinical features of the original tumor are useful models for investigating the mechanism of anaplastic transformation and exploring novel therapeutic strategies.

Cited by 19 publications

References 40 publications

Significant cytostatic effect of everolimus on a gefitinib-resistant anaplastic thyroid cancer cell line harboring PI3KCA gene mutation

Significant cytostatic effect of everolimus on a gefitinib-resistant anaplastic thyroid cancer cell line harboring PI3KCA gene mutation

Establishment and Characterization of Four Novel Thyroid Cancer Cell Lines and PDX Models Expressing the RET/PTC1 Rearrangement, BRAFV600E, or RASQ61R as Drivers

The antitumor effect of metformin with and without carboplatin on primary endometrioid endometrial carcinoma in vivo

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