Characterisation of the novel spontaneously immortalized and invasively growing human skin keratinocyte line HaSKpw

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, c...

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Bibliographic Details
Published in:Scientific reports 2020-09, Vol.10 (1), p.15196, Article 15196
Main Authors: Pavez Lorie, Elizabeth, Stricker, Nicola, Plitta-Michalak, Beata, Chen, I-Peng, Volkmer, Beate, Greinert, Rüdiger, Jauch, Anna, Boukamp, Petra, Rapp, Alexander
Format: Article
Language:English
Subjects:
Antioxidants
Apoptosis
Cancer
Carcinogenesis
Cell Line, Tumor - metabolism
Cell Line, Tumor - pathology
Cell Movement
Chromosomes
Clone Cells
CXCR2 protein
DNA biosynthesis
DNA damage
Fibroblasts
Gene Expression Regulation, Neoplastic
HaCaT Cells
Humans
Keratinocytes - physiology
Keratins, Hair-Specific - genetics
Keratins, Hair-Specific - metabolism
Keratins, Type I - genetics
Keratins, Type I - metabolism
MicroRNAs - genetics
Neoplasm Invasiveness
p53 Protein
Protein-Lysine 6-Oxidase - genetics
Protein-Lysine 6-Oxidase - metabolism
Replication
Resveratrol
S100 Proteins - genetics
S100 Proteins - metabolism
Senescence
Skin - pathology
Skin cancer
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Summary: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.
ISSN:2045-2322
2045-2322
DOI:10.1038/s41598-020-71315-0