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.
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.
Miyazaki
H
H
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.
Fukuda
M
M
Ishijima
Y
Y
Takagi
Y
Y
Iimura
T
T
Negishi
A
A
Hirayama
R
R
Ishikawa
N
N
Amagasa
T
T
Kimura
N
N
D000818:Animals; D002294:Carcinoma, Squamous Cell / Q000201:enzymology* / Q000235:genetics / Q000473:pathology / Q000556:secondary*; D002454:Cell Differentiation / Q000235:genetics; D002455:Cell Division / Q000235:genetics; D002999:Clone Cells; D005260:Female; D006133:Growth Substances / Q000502:physiology*; D006801:Humans; D008175:Lung Neoplasms / Q000201:enzymology* / Q000473:pathology / Q000556:secondary*; D051379:Mice; D008813:Mice, Inbred ICR; D008819:Mice, Nude; D020559:Monomeric GTP-Binding Proteins / Q000096:biosynthesis* / Q000235:genetics; D009062:Mouth Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000473:pathology*; D054778:NM23 Nucleoside Diphosphate Kinases; D009368:Neoplasm Transplantation; D009701:Nucleoside-Diphosphate Kinase / Q000096:biosynthesis* / Q000235:genetics; D014157:Transcription Factors / Q000096:biosynthesis* / Q000235:genetics; D014162:Transfection; D014407:Tumor Cells, Cultured
D006133:Growth Substances; D054778:NM23 Nucleoside Diphosphate Kinases; D014157:Transcription Factors; C517938:NME1 protein, human; C517939:Nme1 protein, mouse; D009701:Nucleoside-Diphosphate Kinase; D020559:Monomeric GTP-Binding Proteins