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Patient-derived tumor xenografts of lung squamous cell carcinoma alter long non-coding RNA profile but not responsiveness to cisplatin

Lung squamous cell carcinoma (LSCC), the second most common type of lung cancer, has received limited attention. Patient-derived tumor xenografts (PDTXs) are useful preclinical models to reproduce the diverse heterogeneity of cancer, but it is important to identify potential variations during their...

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Autores principales: Lu, Dapeng, Luo, Peng, Zhang, Ju, Ye, Yuanyuan, Wang, Qi, Li, Ming, Zhou, Hangcheng, Xie, Mingran, Wang, Baolong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: D.A. Spandidos 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5950531/
https://www.ncbi.nlm.nih.gov/pubmed/29805594
http://dx.doi.org/10.3892/ol.2018.8401
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author Lu, Dapeng
Luo, Peng
Zhang, Ju
Ye, Yuanyuan
Wang, Qi
Li, Ming
Zhou, Hangcheng
Xie, Mingran
Wang, Baolong
author_facet Lu, Dapeng
Luo, Peng
Zhang, Ju
Ye, Yuanyuan
Wang, Qi
Li, Ming
Zhou, Hangcheng
Xie, Mingran
Wang, Baolong
author_sort Lu, Dapeng
collection PubMed
description Lung squamous cell carcinoma (LSCC), the second most common type of lung cancer, has received limited attention. Patient-derived tumor xenografts (PDTXs) are useful preclinical models to reproduce the diverse heterogeneity of cancer, but it is important to identify potential variations during their establishment. A total of 18 PDTXs were established from 37 the surgical specimens and 16 were serially passaged to third generation. Second- and third-generation xenografts had a faster growth rate in mice. The tumor implantation success rate was associated with poorer differentiation, larger tumor volume and higher expression of Ki-67. The xenografts largely retained histological and key immunophenotypic features (including p53, p63, cytokeratin5/6, and E-cadherin). However, increased Ki-67 expression was identified in partial xenografts. Long non-coding RNA (lncRNA) and mRNA expression in third-generation xenografts differed from that of matched primary tumors. Gene Ontology and pathway analysis showed that mRNAs involved in cell cycle, and metabolism regulation were generally upregulated in xenografts, while those associated with immune responses were typically downregulated. Furthermore, the responses of xenografts to cisplatin were consistent with clinical outcome. In the present study, PDTXs of SCC were successfully established, and closely resembled their original tumor regarding their immunophenotype and response to cisplatin. Overall, PDTXS of LSCC altered the lncRNA profile and increased the proliferative activity of cancer cells, whilst retaining responsiveness to cisplatin.
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spelling pubmed-59505312018-05-27 Patient-derived tumor xenografts of lung squamous cell carcinoma alter long non-coding RNA profile but not responsiveness to cisplatin Lu, Dapeng Luo, Peng Zhang, Ju Ye, Yuanyuan Wang, Qi Li, Ming Zhou, Hangcheng Xie, Mingran Wang, Baolong Oncol Lett Articles Lung squamous cell carcinoma (LSCC), the second most common type of lung cancer, has received limited attention. Patient-derived tumor xenografts (PDTXs) are useful preclinical models to reproduce the diverse heterogeneity of cancer, but it is important to identify potential variations during their establishment. A total of 18 PDTXs were established from 37 the surgical specimens and 16 were serially passaged to third generation. Second- and third-generation xenografts had a faster growth rate in mice. The tumor implantation success rate was associated with poorer differentiation, larger tumor volume and higher expression of Ki-67. The xenografts largely retained histological and key immunophenotypic features (including p53, p63, cytokeratin5/6, and E-cadherin). However, increased Ki-67 expression was identified in partial xenografts. Long non-coding RNA (lncRNA) and mRNA expression in third-generation xenografts differed from that of matched primary tumors. Gene Ontology and pathway analysis showed that mRNAs involved in cell cycle, and metabolism regulation were generally upregulated in xenografts, while those associated with immune responses were typically downregulated. Furthermore, the responses of xenografts to cisplatin were consistent with clinical outcome. In the present study, PDTXs of SCC were successfully established, and closely resembled their original tumor regarding their immunophenotype and response to cisplatin. Overall, PDTXS of LSCC altered the lncRNA profile and increased the proliferative activity of cancer cells, whilst retaining responsiveness to cisplatin. D.A. Spandidos 2018-06 2018-03-30 /pmc/articles/PMC5950531/ /pubmed/29805594 http://dx.doi.org/10.3892/ol.2018.8401 Text en Copyright: © Lu et al. This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License (https://creativecommons.org/licenses/by-nc-nd/4.0/) , which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.
spellingShingle Articles
Lu, Dapeng
Luo, Peng
Zhang, Ju
Ye, Yuanyuan
Wang, Qi
Li, Ming
Zhou, Hangcheng
Xie, Mingran
Wang, Baolong
Patient-derived tumor xenografts of lung squamous cell carcinoma alter long non-coding RNA profile but not responsiveness to cisplatin
title Patient-derived tumor xenografts of lung squamous cell carcinoma alter long non-coding RNA profile but not responsiveness to cisplatin
title_full Patient-derived tumor xenografts of lung squamous cell carcinoma alter long non-coding RNA profile but not responsiveness to cisplatin
title_fullStr Patient-derived tumor xenografts of lung squamous cell carcinoma alter long non-coding RNA profile but not responsiveness to cisplatin
title_full_unstemmed Patient-derived tumor xenografts of lung squamous cell carcinoma alter long non-coding RNA profile but not responsiveness to cisplatin
title_short Patient-derived tumor xenografts of lung squamous cell carcinoma alter long non-coding RNA profile but not responsiveness to cisplatin
title_sort patient-derived tumor xenografts of lung squamous cell carcinoma alter long non-coding rna profile but not responsiveness to cisplatin
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5950531/
https://www.ncbi.nlm.nih.gov/pubmed/29805594
http://dx.doi.org/10.3892/ol.2018.8401
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