Activated leukocyte cell adhesion molecule (ALCAM/CD166/MEMD) could function as a cell surface sensor for cell density, controlling the transition between local cell proliferation and tissue invasion in melanoma progression. We have tested the hypothesis that progressive cell clustering controls the proteolytic cascade for activation of gelatinase A/matrix metalloproteinase-2 (MMP-2), which involves formation of an intermediate ternary complex of membrane type 1 MMP (MT1-MMP/MMP-14), tissue inhibitor of metalloproteinase-2 (TIMP-2), and pro-MMP-2 at the cell surface. Surprisingly, truncation of ALCAM severely impaired MMP-2 activation in a nude mouse xenograft model, in which we previously observed diminished primary tumor growth and enhanced melanoma metastasis.
View Article and Find Full Text PDFPreviously, we reported the identification of MMA1A by screening for differential gene expression in two human melanoma cell lines displaying diverse metastatic behavior after subcutaneous inoculation into nude mice. Splice variant MMA1B, which also was identified through database homology searches, showed a high degree of similarity with the MMA1A for exons 1, 2, and 4, but was missing exon 3. Through extensive expression profiling among normal and tumor samples, both MMA1A and -1B were found to belong to the family of cancer-testis antigens.
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