Document Detail

T-cadherin loss induces an invasive phenotype in human keratinocytes and squamous cell carcinoma (SCC) cells in vitro and is associated with malignant transformation of cutaneous SCC in vivo.
MedLine Citation:
PMID:  20394625     Owner:  NLM     Status:  In-Process    
BACKGROUND: Cadherins play important roles in controlling keratinocyte growth, differentiation and survival. Atypical glycosylphosphatidylinositol-anchored T-cadherin (T-cad) is highly expressed in the basal keratinocyte layer of skin. The role of T-cad in keratinocyte biology and pathology is unclear.
OBJECTIVES: To define the role of T-cad in the pathogenesis of cutaneous squamous cell carcinoma (SCC) through gain-of-function and loss-of-function studies in vitro and through examination of T-cad expression patterns in human cutaneous SCC specimens in relation to histological classification of degree of tumour differentiation.
METHODS: In vitro studies employed lentiviral-mediated overexpression/silencing of T-cad in normal human keratinocyte (HaCaT) and SCC (A431) cell lines, monolayer and multicellular spheroid culture models, cell morphology analyses and assays of random motility and invasion. Immunohistochemistry was performed on skin specimens from patients with actinic keratosis, Bowen disease or SCC.
RESULTS: In vitro, silencing of T-cad induced a morphologically elongated and disorganized cell phenotype, increased random motility and markedly enhanced invasive potential. Overexpression of T-cad induced a morphologically spread and compact cell phenotype and blunted invasive potential. In vivo, regional loss of T-cad expression was more frequent and prominent in SCC classified as moderately-to-poorly differentiated than in SCC classified as well differentiated. However, in both categories aberrant and/or absence of T-cad expression was associated with histological features of a potentially more malignant and invasive phenotype of cutaneous SCC.
CONCLUSIONS: T-cad is a controlling determinant of SCC phenotype and invasive behaviour and its loss is associated with the process of malignant transformation from noninvasive to invasive SCC.
D Pfaff; M Philippova; S A Buechner; K Maslova; T Mathys; P Erne; T J Resink
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-04-12
Journal Detail:
Title:  The British journal of dermatology     Volume:  163     ISSN:  1365-2133     ISO Abbreviation:  Br. J. Dermatol.     Publication Date:  2010 Aug 
Date Detail:
Created Date:  2010-07-29     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0004041     Medline TA:  Br J Dermatol     Country:  England    
Other Details:
Languages:  eng     Pagination:  353-63     Citation Subset:  IM    
Department of Biomedicine, Laboratory for Signal Transduction, Lab. 316, Basel University Hospital, CH 4031 Basel, Switzerland.
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