Abstract
We here present the spontaneously immortalised cell line, HaSKpw, as a novel model for the multistep process of skin carcinogenesis. HaSKpw cells were established from the epidermis of normal human adult skin that, without crisis, are now growing unrestricted and feeder-independent. At passage 22, clonal populations were established and clone7 (HaSKpwC7) was further compared to the also spontaneously immortalized HaCaT cells. As important differences, the HaSKpw cells express wild-type p53, remain pseudodiploid, and show a unique chromosomal profile with numerous complex aberrations involving chromosome 20. In addition, HaSKpw cells overexpress a pattern of genes and miRNAs such as KRT34, LOX, S100A9, miR21, and miR155; all pointing to a tumorigenic status. In concordance, HaSKpw cells exhibit reduced desmosomal contacts that provide them with increased motility and a highly migratory/invasive phenotype as demonstrated in scratch- and Boyden chamber assays. In 3D organotypic cultures, both HaCaT and HaSKpw cells form disorganized epithelia but only the HaSKpw cells show tumorcell-like invasive growth. Together, HaSKpwC7 and HaCaT cells represent two spontaneous (non-genetically engineered) “premalignant” keratinocyte lines from adult human skin that display different stages of the multistep process of skin carcinogenesis and thus represent unique models for analysing skin cancer development and progression.
Highlights
We here present the spontaneously immortalised cell line, HaSKpw, as a novel model for the multistep process of skin carcinogenesis
Many keratinocyte cell lines used in dermatological research are based on immortalization by either SV402–6 or HPV7 and later by introducing the hTERT gene, when it was clear that telomerase activation was required for continuous growth[8]
While investigations of skin biopsies and tumour material reflect the interindividual variations of cutaneous squamous-cell carcinomas (cSCC) the use of immortalised cell lines as a tool to study the onset and progression of skin cancer has made it possible to truly explore different pathways involved in these processes under stable and reproducible conditions[41]
Summary
We here present the spontaneously immortalised cell line, HaSKpw, as a novel model for the multistep process of skin carcinogenesis. HaSKpwC7 and HaCaT cells represent two spontaneous (non-genetically engineered) “premalignant” keratinocyte lines from adult human skin that display different stages of the multistep process of skin carcinogenesis and represent unique models for analysing skin cancer development and progression. The spontaneously immortalized HaCaT cell line was derived from adult trunk s kin[11] and may represent a different evolutionary pathway. And different from most other cell lines, in particular the HaCaT cells, the HaSKpw cells, which were established from “normal” skin keratinocytes without any sign of growth retardation or crisis present a unique spectrum of genetic and growth properties. As these cells were not genetically engineered, they may well add to an unbiased view of the broad spectrum of early genetic events occurring in naïve human skin and contributing to the genetic heterogeneity of AKs and cSCCs
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