A Unique Panel of Patient-Derived Cutaneous Squamous Cell Carcinoma Cell Lines Provides a Preclinical Pathway for Therapeutic Testing.
Animals
Antineoplastic Agents
/ pharmacology
Biomarkers, Tumor
Biopsy
Carcinoma, Squamous Cell
/ genetics
Cell Line, Tumor
Disease Models, Animal
Drug Evaluation, Preclinical
/ methods
Gene Expression Profiling
Humans
Immunohistochemistry
Keratinocytes
/ drug effects
Male
Mutation
Neoplasm Metastasis
Neoplasm Staging
Skin Neoplasms
/ genetics
Xenograft Model Antitumor Assays
cutaneous
in vitro
keratinocytes
squamous cell carcinoma
Journal
International journal of molecular sciences
ISSN: 1422-0067
Titre abrégé: Int J Mol Sci
Pays: Switzerland
ID NLM: 101092791
Informations de publication
Date de publication:
12 Jul 2019
12 Jul 2019
Historique:
received:
11
06
2019
revised:
28
06
2019
accepted:
04
07
2019
entrez:
25
7
2019
pubmed:
25
7
2019
medline:
28
12
2019
Statut:
epublish
Résumé
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. 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. 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. 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.
Sections du résumé
BACKGROUND
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
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
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
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.
Identifiants
pubmed: 31336867
pii: ijms20143428
doi: 10.3390/ijms20143428
pmc: PMC6678499
pii:
doi:
Substances chimiques
Antineoplastic Agents
0
Biomarkers, Tumor
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Cancer Research UK
ID : 13044
Pays : United Kingdom
Organisme : European Research Council
ID : 250170
Pays : International
Organisme : CRUK Beatson Institute
ID : C596/A17196
Organisme : Biotechnology and Biological Sciences Research Council
ID : 1906000
Pays : United Kingdom
Organisme : Cancer Research UK
ID : A13044
Pays : United Kingdom
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