Overexpression of melanoma inhibitory activity (MIA) enhances extravasation and metastasis of A-mel 3 melanoma cells in vivo

The secreted MIA protein is strongly expressed by advanced primary and meta static melanomas but not in normal melanocytes. Previous studies have shown that MIA serum levels correlate with clinical tumour progression in melano ma patients. To provide direct evidence that MIA plays a role in metastasis of malignant melanomas, A-mel 3 hamster melanoma cells were transfected wi th sense- and antisense rhMIA cDNA and analysed subsequently for changes in their tumorigenic and metastatic potential. Enforced expression of MIA in A-mel 3 cells significantly increased their metastatic potential without af fecting primary tumour growth, cell proliferation or apoptosis rate in hams ters, compared with control or antisense transfected cells. Additionally, M IA overexpressing transfectants showed a higher rate of both tumour cell in vasion and extravasation. Cells transfected with MIA antisense generally ex erted an opposite response. The above changes in function attributed to the expression of MIA may underlie the contribution of MIA to the malignant ph enotype, (C) 2000 Cancer Research Campaign.