IDENTIFICATION OF MELANOMA INHIBITORY ACTIVITY AND OTHER DIFFERENTIALLY EXPRESSED MESSENGER-RNAS IN HUMAN-MELANOMA CELL-LINES WITH DIFFERENT METASTATIC CAPACITY BY MESSENGER-RNA DIFFERENTIAL DISPLAY

The differential display technique was used to identify mRNAs differen tially expressed in human melanoma cell lines with different metastati c capacity. We report the isolation of nine different clones, of which four were uniquely expressed in the highly metastatic human melanoma cell line MV3, whereas the other five clones were uniquely expressed i n the poorly metastatic human melanoma cell Line 530. The differences in expression identified by differential mRNA display were confirmed b y Northern blot analyses. DNA sequencing followed by computer search a nalyses indicated that of the nine differentially expressed clones, fi ve represented novel gene products, The other four were histocompatibi lity antigen HLA-DR, laminin B-2, melanoma inhibitory activity (MIA), and tissue inhibitor of metalloproteinases 3. MIA was also identified in RNA from human melanoma metastasis lesions in a comparison by diffe rential display with pooled human nevi, Northern blot analysis confirm ed MIA mRNA expression in nonmetastasizing melanoma cell lines and in melanoma metastasis lesions, while expression was absent in highly met astasizing cell Lines and pretumor stages. In the 11 metastasis lesion s examined, MIA mRNA expression was apparently inversely correlated wi th pigmentation.