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 inculture

The metastasis suppressor activity of nm23/nucleoside diphosphate (NDP) kin ase was assessed using human oral squamous cell carcinoma (SCC) cell lines. When the expression of mm23/NDP kinase was compared among several SCC cell lines, nm23-H2/NDP kinase B gene product, but not nm23-H1/NDP kinase A gen e product, was reduced in the metastatic cells, Transfection of nm23-H2 int o the metastatic SCC cell line LMF4 caused reduction in the lung metastasis in an experimental metastasis assay. A histological analysis of the pulmon ary metastatic foci revealed that although foci of the control clones were composed of anaplastic squamous cells, those of the nm23-H2-transfected clo nes consisted of mostly well-differentiated cells mimicking normal stratifi ed epithelial constitution. The transfected cells were morphologically indi stinguishable 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 pl atelet-derived growth factor, insulin-like growth factor I, and insulin, al though both clones retained sensitivity to transferrin, These results demon strate that nm23-H2 protein does have metastasis suppressor activity for hu man SCC cells and suggest that this activity may be elicited by modulating growth and/or differentiation potential in response to environmental factor s.