The
cell surface glycoprotein MUC18MCAM/CD146 was originally defined as a marker of
melanoma progression and has been suspected to be directly linked to the metastatic process of this
malignancy. In order to address this question, 2 MCAM negative human
melanoma cell lines, SK-2 and XP44RO(Mel), were transfected with MCAM-encoding
cDNA. Surface MCAM expression on SK-2 and XP44RO(Mel) transfectants was similar to that observed in naturally occurring MCAM positive human
melanoma cells and transfectants demonstrated MCAM-dependent increase in homotypic adhesion in vitro. The growth behavior of 7 MCAM transfectants and their respective vector controls was evaluated in SCID mice.
Tumor size at 4-5 weeks after s.c. implantation was highly variable, but did not correlate with MCAM expression. Despite massive primary
tumor formation at the injection site, no spontaneous
metastasis was observed with any of the investigated MCAM transfectants. The influence of MCAM expression on lung
metastases formation in an experimental
metastasis assay was system dependent, converting only XP44RO(Mel) transfectants into metastatic cells, although increased homotypic adhesion, leading to formation of
tumor cell clusters, was observed with transfectants of both cell lines in vitro. Our findings indicate that MCAM expression of human
melanoma cells has an influence on later stages of the metastatic process only, namely, extravasation and establishment of new foci of growth, but is per se not sufficient for this process.