Ectopic coexpression of keratin 8 and 18 promotes invasion of transformed keratinocytes and is induced in patients with cutaneous squamous cell carcinoma

abstract Cutaneous squamous cell carcinoma (cSCC) results from transformation of epidermal keratinocytes. Inva-sion of transformed keratinocytes through the basement membrane into the dermis results in invasivecSCC with substantial metastatic potential. To better understand the mechanisms for invasion and metas-tasis, we compared the protein expression profiles of a non-metastatic transformed mouse keratinocyteline and its metastatic derivative. Keratin 8 (Krt8) and Krt18, not seen in normal keratinocytes, werecoexpressed and formed Krt8/18 filaments in the metastatic line. The metastatic line efficiently invadedan artificial basement membrane in vitro owing to the Krt8/18-coexpression, since coexpression of exog-enous Krt8/18 in the non-invasive parental line conferred invasiveness. To test whether the Krt8/18-coexpression is induced and is involved in cSCC invasion, we examined specimens from 21 pre-invasiveand 24 invasive cSCC patients by immunohistochemistry, and the ectopic Krt8/18-coexpression wasalmost exclusively found in invasive cSCC. Further studies are needed to examine the clinical significanceof ectopic Krt8/18-coexpression in cSCC. 2010 Elsevier Inc. All rights reserved.