A Unique Panel of Patient-Derived Cutaneous Squamous Cell Carcinoma Cell Lines Provides a Preclinical Pathway for Therapeutic Testing

Sakinah Hassan, Karin J Purdie, Jun Wang, Catherine A Harwood, Charlotte M Proby, Celine Pourreyron, Nikol Mladkova, Ai Nagano, Sandeep Dhayade, Dimitris Athineos, Matthew Caley, Viviana Mannella, Karen Blyth, Gareth J Inman, Irene M Leigh (Lead / Corresponding author)

Research output: Contribution to journalArticle

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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.

Original languageEnglish
Article number3428
Pages (from-to)1-26
Number of pages26
JournalInternational Journal of Molecular Sciences
Volume20
Issue number14
DOIs
Publication statusPublished - 12 Jul 2019

Fingerprint

cultured cells
Squamous Cell Carcinoma
cancer
Cells
Cell Line
Skin
experimentation
Testing
Exome
Preclinical Drug Evaluations
Microsatellite Repeats
Screening
drugs
Therapeutics
screening
Inborn Genetic Diseases
sequencing
mortality
metastasis
Growth

Keywords

  • Cutaneous
  • In vitro
  • Keratinocytes
  • Squamous cell carcinoma

Cite this

Hassan, Sakinah ; Purdie, Karin J ; Wang, Jun ; Harwood, Catherine A ; Proby, Charlotte M ; Pourreyron, Celine ; Mladkova, Nikol ; Nagano, Ai ; Dhayade, Sandeep ; Athineos, Dimitris ; Caley, Matthew ; Mannella, Viviana ; Blyth, Karen ; Inman, Gareth J ; Leigh, Irene M. / A Unique Panel of Patient-Derived Cutaneous Squamous Cell Carcinoma Cell Lines Provides a Preclinical Pathway for Therapeutic Testing. In: International Journal of Molecular Sciences. 2019 ; Vol. 20, No. 14. pp. 1-26.
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title = "A Unique Panel of Patient-Derived Cutaneous Squamous Cell Carcinoma Cell Lines Provides a Preclinical Pathway for Therapeutic Testing",
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.",
keywords = "Cutaneous, In vitro, Keratinocytes, Squamous cell carcinoma",
author = "Sakinah Hassan and Purdie, {Karin J} and Jun Wang and Harwood, {Catherine A} and Proby, {Charlotte M} and Celine Pourreyron and Nikol Mladkova and Ai Nagano and Sandeep Dhayade and Dimitris Athineos and Matthew Caley and Viviana Mannella and Karen Blyth and Inman, {Gareth J} and Leigh, {Irene M}",
note = "Funding: This research was funded by Cancer Research UK, Programme grants 1989–2017 number A13044, European Research Council Advanced Investigation Award IL (250170), BBSRC iCASE Studentship QMUL/ Biosceptre (UK) Ltd. and CRUK Beatson Institute C596/A17196",
year = "2019",
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Hassan, S, Purdie, KJ, Wang, J, Harwood, CA, Proby, CM, Pourreyron, C, Mladkova, N, Nagano, A, Dhayade, S, Athineos, D, Caley, M, Mannella, V, Blyth, K, Inman, GJ & Leigh, IM 2019, 'A Unique Panel of Patient-Derived Cutaneous Squamous Cell Carcinoma Cell Lines Provides a Preclinical Pathway for Therapeutic Testing', International Journal of Molecular Sciences, vol. 20, no. 14, 3428, pp. 1-26. https://doi.org/10.3390/ijms20143428

A Unique Panel of Patient-Derived Cutaneous Squamous Cell Carcinoma Cell Lines Provides a Preclinical Pathway for Therapeutic Testing. / Hassan, Sakinah; Purdie, Karin J; Wang, Jun; Harwood, Catherine A; Proby, Charlotte M; Pourreyron, Celine; Mladkova, Nikol; Nagano, Ai; Dhayade, Sandeep; Athineos, Dimitris; Caley, Matthew; Mannella, Viviana; Blyth, Karen; Inman, Gareth J; Leigh, Irene M (Lead / Corresponding author).

In: International Journal of Molecular Sciences, Vol. 20, No. 14, 3428, 12.07.2019, p. 1-26.

Research output: Contribution to journalArticle

TY - JOUR

T1 - A Unique Panel of Patient-Derived Cutaneous Squamous Cell Carcinoma Cell Lines Provides a Preclinical Pathway for Therapeutic Testing

AU - Hassan, Sakinah

AU - Purdie, Karin J

AU - Wang, Jun

AU - Harwood, Catherine A

AU - Proby, Charlotte M

AU - Pourreyron, Celine

AU - Mladkova, Nikol

AU - Nagano, Ai

AU - Dhayade, Sandeep

AU - Athineos, Dimitris

AU - Caley, Matthew

AU - Mannella, Viviana

AU - Blyth, Karen

AU - Inman, Gareth J

AU - Leigh, Irene M

N1 - Funding: This research was funded by Cancer Research UK, Programme grants 1989–2017 number A13044, European Research Council Advanced Investigation Award IL (250170), BBSRC iCASE Studentship QMUL/ Biosceptre (UK) Ltd. and CRUK Beatson Institute C596/A17196

PY - 2019/7/12

Y1 - 2019/7/12

N2 - 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.

AB - 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.

KW - Cutaneous

KW - In vitro

KW - Keratinocytes

KW - Squamous cell carcinoma

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U2 - 10.3390/ijms20143428

DO - 10.3390/ijms20143428

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VL - 20

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EP - 26

JO - International Journal of Molecular Sciences

JF - International Journal of Molecular Sciences

SN - 1661-6596

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