Document Detail

Cell activation via CD44 occurs in advanced stages of squamous cell carcinogenesis.
MedLine Citation:
PMID:  10783309     Owner:  NLM     Status:  MEDLINE    
Squamous cell carcinoma (SCC) derives from dysplastic or metaplastic stratified epithelia. The process of squamous cell carcinogenesis has been investigated for the potential role of the adhesion molecule CD44, whose standard form (CD44s) and isoforms generated by alternative splicing of variant exons are known to display altered expression during tumorigenesis in other systems. We have utilized an in vitro correlate of squamous cell carcinogenesis, in which progression stages from normal squamous epithelium to dysplastic lesions and to SCC are represented by primary cultures of normal keratinocytes, by human papilloma virus-immortalized keratinocytes (UP) and by HPVimmortalized/v-Ha-ras transfected tumorigenic keratinocytes (UPR). We investigated expression of CD44 and of variant isoforms, from mRNA to intracellular and surface protein levels, and found no relationship between expression of CD44 and stages of squamous cell carcinogenesis. However, when the function of CD44 was analyzed as Ca(2+) mobilization ability upon monoclonal antibody binding and crosslinking, signal transduction via CD44 was found only for the neoplastic stage (UPR cells). Ca(2+) mobilization was completely independent of density of surface CD44. We have performed similar analyses in an in vitro model of SCC in which four squamous tumor cell lines and UPR cells were sorted according to increasing resistance to external cytotoxic stimuli, i.e. starving conditions, treatment with the retinoid N-(4-hydroxyphenyl)retinamide and cytolytic activity of effector lymphokine-activated killer cells. No relationship between expression of CD44 and level of cell resistance against external cell death-inducing stimuli was found, while CD44-mediated Ca(2+) mobilization ability was restricted to the highly resistant tumor cell lines. Our results indicate that the role(s) of CD44 in squamous cell proliferative disorders can be evinced from the functional features of the molecule, rather than from its phenotypic repertoire.
S Bruno; M Fabbi; M Tiso; B Santamaria; F Ghiotto; D Saverino; C Tenca; D Zarcone; S Ferrini; E Ciccone; C E Grossi
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Carcinogenesis     Volume:  21     ISSN:  0143-3334     ISO Abbreviation:  Carcinogenesis     Publication Date:  2000 May 
Date Detail:
Created Date:  2000-06-15     Completed Date:  2000-06-15     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  8008055     Medline TA:  Carcinogenesis     Country:  ENGLAND    
Other Details:
Languages:  eng     Pagination:  893-900     Citation Subset:  IM    
Section of Human Anatomy and Section of Biochemistry, Department of Experimental Medicine, University of Genoa, Via De Toni 14, 16132 Genoa, Italy.
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MeSH Terms
Antigens, CD44 / genetics*,  metabolism
Base Sequence
Calcium / metabolism
Carcinoma, Squamous Cell / metabolism,  pathology*
Cell Line, Transformed
Cell Transformation, Neoplastic
DNA Primers
Signal Transduction
Tumor Cells, Cultured
Reg. No./Substance:
0/Antigens, CD44; 0/DNA Primers; 7440-70-2/Calcium

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