Document Detail

Autocrine motility-stimulatory pathways of oral premalignant lesion cells.
MedLine Citation:
PMID:  17370039     Owner:  NLM     Status:  MEDLINE    
Patients with premalignant oral lesions have varying levels of risk of developing oral squamous cell carcinoma (OSCC), whose aggressiveness requires increased motility. Not known is if and how premalignant oral lesion cells acquire the increased motility characteristic of OSCC. This was addressed by immunohistochemical analysis of banked premalignant lesion tissues and by functional analyses using cultures established from premalignant oral lesions and OSCC. These studies showed premalignant oral lesion cells and OSCC to be more motile than normal keratinocytes. Concomitantly, levels of ceramide were reduced. The activity of the protein phosphatase PP-2A, which restricts motility and which can be activated by ceramide, was also diminished. This was due to IL-10 released from premalignant lesion cells. Treatment with a membrane-permeable ceramide restored PP-2A activity and blocked migration. These studies show an autocrine motility-stimulatory pathway that is mediated in premalignant lesion cells by IL-10 through its reduction of ceramide levels and inhibition of PP-2A activity.
M Rita I Young; Brad W Neville; Angela C Chi; Deanne M R Lathers; M Boyd Gillespie; Terry A Day
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, U.S. Gov't, Non-P.H.S.     Date:  2007-03-17
Journal Detail:
Title:  Clinical & experimental metastasis     Volume:  24     ISSN:  0262-0898     ISO Abbreviation:  Clin. Exp. Metastasis     Publication Date:  2007  
Date Detail:
Created Date:  2007-04-26     Completed Date:  2007-06-25     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  8409970     Medline TA:  Clin Exp Metastasis     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  131-9     Citation Subset:  IM    
Research Service 151, Ralph H. Johnson VA Medical Center, Ralph H. Johnson Veterans Affairs Hospital, Charleston, SC 29401-5799, USA.
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MeSH Terms
Blotting, Western
Carcinoma, Squamous Cell / enzymology,  metabolism,  pathology*
Cell Movement
Ceramides / metabolism
Interleukin-10 / pharmacology
Mouth Neoplasms / enzymology,  metabolism,  pathology*
Phosphoprotein Phosphatases / metabolism
Precancerous Conditions / enzymology,  metabolism,  pathology*
Grant Support
Reg. No./Substance:
0/Ceramides; 130068-27-8/Interleukin-10; EC Phosphatases

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