Document Detail

Overexpression of nm23-H2/NDP kinase B in a human oral squamous cell carcinoma cell line results in reduced metastasis, differentiated phenotype in the metastatic site, and growth factor-independent proliferative activity in culture.
MedLine Citation:
PMID:  10632374     Owner:  NLM     Status:  MEDLINE    
The metastasis suppressor activity of nm23/nucleoside diphosphate (NDP) kinase was assessed using human oral squamous cell carcinoma (SCC) cell lines. When the expression of nm23/NDP kinase was compared among several SCC cell lines, nm23-H2/NDP kinase B gene product, but not nm23-HI/NDP kinase A gene product, was reduced in the metastatic cells. Transfection of nm23-H2 into the metastatic SCC cell line LMF4 caused reduction in the lung metastasis in an experimental metastasis assay. A histological analysis of the pulmonary metastatic foci revealed that although foci of the control clones were composed of anaplastic squamous cells, those of the nm23-H2-transfected clones consisted of mostly well-differentiated cells mimicking normal stratified epithelial constitution. The transfected cells were morphologically indistinguishable from the control ones in culture, but they differed from each other in that the former cells proliferated faster than the latter, became less serum dependent, and lost responsiveness to growth factors such as platelet-derived growth factor, insulin-like growth factor I, and insulin, although both clones retained sensitivity to transferrin. These results demonstrate that nm23-H2 protein does have metastasis suppressor activity for human SCC cells and suggest that this activity may be elicited by modulating growth and/or differentiation potential in response to environmental factors.
H Miyazaki; M Fukuda; Y Ishijima; Y Takagi; T Iimura; A Negishi; R Hirayama; N Ishikawa; T Amagasa; N Kimura
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Clinical cancer research : an official journal of the American Association for Cancer Research     Volume:  5     ISSN:  1078-0432     ISO Abbreviation:  Clin. Cancer Res.     Publication Date:  1999 Dec 
Date Detail:
Created Date:  2000-02-14     Completed Date:  2000-02-14     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  9502500     Medline TA:  Clin Cancer Res     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  4301-7     Citation Subset:  IM    
Department of Gene Regulation and Protein Function, Tokyo Metropolitan Institute of Gerontology, First Department of Oral and Maxillofacial Surgery, Tokyo Medical and Dental University, Japan.
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MeSH Terms
Carcinoma, Squamous Cell / enzymology*,  genetics,  pathology,  secondary*
Cell Differentiation / genetics
Cell Division / genetics
Clone Cells
Growth Substances / physiology*
Lung Neoplasms / enzymology*,  pathology,  secondary*
Mice, Inbred ICR
Mice, Nude
Monomeric GTP-Binding Proteins / biosynthesis*,  genetics
Mouth Neoplasms / enzymology*,  genetics,  pathology*
NM23 Nucleoside Diphosphate Kinases
Neoplasm Transplantation
Nucleoside-Diphosphate Kinase / biosynthesis*,  genetics
Transcription Factors / biosynthesis*,  genetics
Tumor Cells, Cultured
Reg. No./Substance:
0/Growth Substances; 0/NM23 Nucleoside Diphosphate Kinases; 0/Transcription Factors; EC protein, human; EC protein, mouse; EC Kinase; EC GTP-Binding Proteins

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