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.

Cutaneous Squamous Cell Carcinoma: From Biology to Therapy

“…The role of p53 in ultraviolet B-induced carcinogenesis has been confirmed in p53 −/− mice, which have an increased propensity for developing AK lesions and CSCCs secondary to ultraviolet B (UVB) exposure [36,37]. Furthermore, several groups have confirmed the presence of p53 mutations in CSCC cell lines [38,39]. P53 mutations are an early event in CSCC development and are ultimately responsible for great genomic instability.…”

Comprehensive Mutational and Phenotypic Characterization of New Metastatic Cutaneous Squamous Cell Carcinoma Cell Lines Reveal Novel Drug Susceptibilities

“…Cell lines remain powerful pre-clinical tools to study biological behavior, as well as being amenable to high-throughput drug screening [ 20 , 21 , 22 ]. Cell lines derived from primary cSCC have been reported [ 23 , 24 , 25 , 26 , 27 , 28 ], but there are few cell lines derived from metastatic cSCC ( Table S1 ). The metastatic cell lines UT-SCC7, UT-SCC59A, and UT-SCC115 have not been validated molecularly, nor has evidence of tumorigenicity been published.…”

RIPK1‐mediated immunogenic cell death promotes anti‐tumour immunity against soft‐tissue sarcoma

“…In fact, ILP‐TNF/Mel can achieve a limb salvage rate of 80% in such patients with a 2‐year overall progression‐free survival of 67%. Accordingly, cell lines derived from patients with such malignancies (Hassan et al , ) are sensitive to TNF/SM‐induced cell death that is caspase‐dependent (Figs L–N and EV2L–N). Together, our observations indicate that SM sensitises extremity malignancies to TNF‐induced cell death, suggesting that it might be beneficial to incorporate SM into current ILP‐TNF/Mel, standard‐of‐care treatment regimens.…”