SUPPRESSION OF HUMAN-MELANOMA METASTASIS FOLLOWING INTRODUCTION OF CHROMOSOME-6 IS INDEPENDENT OF NME1 (NM23)

Metastasis is suppressed more than 95% following microcell-mediated tr ansfer of a single copy of neomycin-tagged human chromosome 6 (neo6) i nto the human melanoma cell lines C8161 and MelJuSo, Concomitant with metastasis suppression is upregulation of NME1 (Nm23-H1) mRNA and prot ein expression, The purposes of this study were to determine whether N ME1 expression was responsible for metastasis suppression in neo6/mela noma hybrids, and whether genes on chromosome 6 regulate NME1, Using n eo6/C8161 cells, transfection of CAT reporter constructs linked to the NME1 promoter failed to consistently induce CAT, Therefore, it does n ot appear that genes on chromosome 6 directly control transcription of NME1, Transfection and overexpression of NME1 in MelJuSo, under the c ontrol of the CMV promoter, resulted in 40-80% inhibition of lung meta stasis following i,v, inoculation of 2 x 10(5) cells, Only one transfe ctant of C8161 subclone 9 (C8161cl.9) cells was suppressed for metasta sis. Control transfections,vith pCMVneo or pSV2neo did not suppress me tastasis in either cell line, Taken together, these data suggest that NME1 can reduce metastatic potential of some human melanoma cells; but , this inhibitory activity appears to be independent of the metastasis suppression following introduction of chromosome 6 into C8161 and Mel JuSo human melanoma cell lines.