Cutaneous squamous cell carcinoma (cSCC) accounts for most keratinocyte cancer deaths due to its ability to metastasise in approximately 5 % of cases. Despite this, treatments beyond surgery are poorly defined, especially for the immunosuppressed cohort at high risk of cSCC development. Identifying and translating candidate therapeutics to the clinical setting is largely hindered by the lack of well-characterised and reliable preclinical cSCC cell lines to model disease in vitro. The few cell lines that are available scarcely capture the genetic complexity and inter-patient heterogeneity of cSCC.
To this end, this study phenotypically characterised a novel pair of matched cell lines derived from an immunosuppressed patients’ primary and coincident lymph node cSCC tumours, denoted UW-CSCC3-P and UW-CSCC3-M, respectively. It describes their characteristics in both two-dimensional and three-dimensional culture, including growth rate, migration, invasion, spheroid formation and radiosensitivity. Subtle differences were observed between the two cell lines, and the elucidated phenotypic profiles appear distinct from previously reported cSCC cell lines, especially those derived from immunocompetent patients’ tumours.
To demonstrate their experimental utility, UW-CSCC3-P and UW-CSCC3-M were subsequently used for screening of several phosphoinositide 3-kinase (PI3K) inhibitors including both pan-inhibitors and subunit specific inhibitors. Sensitivity varied greatly between individual drugs tested, and dual PI3K/mTOR inhibitors were notably ineffective against these cell lines. All PI3K inhibitors screened were less potent against UW-CSCC3-P and UW-CSCC3-M than they were against previously reported cSCC cultures with different PI3K-related mutational profiles.
Together, these findings exemplify the need for sustained therapeutic screening in an expanded panel of cSCC cell lines such as those described here. Such efforts will ensure inter-tumour variability is better captured at the in vitro level for deeper understandings of cSCC biology and therapeutic response across the entire cSCC cohort. UW-CSCC3-P and UW-CSCC3-M represent important progress in this regard, and demonstrate their value as an in vitro tool to investigate cSCC progression from primary to metastatic disease, as well as therapeutic response in the context of patient immunosuppression.