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Targeted Therapy Against the Cell of Origin in Cutaneous Squamous Cell Carcinoma
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A Unique Panel of Patient-Derived Cutaneous Squamous Cell Carcinoma Cell Lines Provides a Preclinical Pathway for Therapeutic Testing

1
Blizard Institute, Barts and the London School of Medicine and Dentistry, QMUL, London E1 2AT, UK
2
Barts Cancer Institute, QMUL, London EC1M 6BQ, UK
3
Division of Cancer, Ninewells Hospital and Medical School, University of Dundee, Dundee DD1 9SY, UK
4
Cancer Research UK Beatson Institute, Garscube Estate, Switchback Rd, Glasgow G61 1BD, UK
5
Institute of Cancer Sciences, University of Glasgow, Glasgow G61 1GH, UK
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2019, 20(14), 3428; https://doi.org/10.3390/ijms20143428
Received: 11 June 2019 / Revised: 28 June 2019 / Accepted: 4 July 2019 / Published: 12 July 2019
(This article belongs to the Special Issue Molecular Aspects of Cutaneous Squamous Cell Carcinoma)
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Abstract

Background: Cutaneous squamous cell carcinoma (cSCC) incidence continues to rise with increasing morbidity and mortality, with limited treatment options for advanced disease. Future improvements in targeted therapy will rely on advances in genomic/transcriptomic understanding and the use of model systems for basic research. We describe here the panel of 16 primary and metastatic cSCC cell lines developed and characterised over the past three decades in our laboratory in order to provide such a resource for future preclinical research and drug screening. Methods: Primary keratinocytes were isolated from cSCC tumours and metastases, and cell lines were established. These were characterised using short tandem repeat (STR) profiling and genotyped by whole exome sequencing. Multiple in vitro assays were performed to document their morphology, growth characteristics, migration and invasion characteristics, and in vivo xenograft growth. Results: STR profiles of the cSCC lines allow the confirmation of their unique identity. Phylogenetic trees derived from exome sequence analysis of the matched primary and metastatic lines provide insight into the genetic basis of disease progression. The results of in vivo and in vitro analyses allow researchers to select suitable cell lines for specific experimentation. Conclusions: There are few well-characterised cSCC lines available for widespread preclinical experimentation and drug screening. The described cSCC cell line panel provides a critical tool for in vitro and in vivo experimentation. View Full-Text
Keywords: squamous cell carcinoma; cutaneous; in vitro; keratinocytes squamous cell carcinoma; cutaneous; in vitro; keratinocytes
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Hassan, S.; Purdie, K.J.; Wang, J.; Harwood, C.A.; Proby, C.M.; Pourreyron, C.; Mladkova, N.; Nagano, A.; Dhayade, S.; Athineos, D.; Caley, M.; Mannella, V.; Blyth, K.; Inman, G.J.; Leigh, I.M. A Unique Panel of Patient-Derived Cutaneous Squamous Cell Carcinoma Cell Lines Provides a Preclinical Pathway for Therapeutic Testing. Int. J. Mol. Sci. 2019, 20, 3428.

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