Functional role of melanoma inhibitory activity in regulating invasion and metastasis of malignant melanoma cells in vivo.

MIA (melanoma inhibitory activity) has been previously isolated from the tissue culture supernatant of melanoma cell lines as an autoregulatory activity, inhibiting thymidine incorporation. However, subsequent analyses of melanocytic tumours in vivo have correlated enhanced MIA expression with progression of melanocytic tumours, conflicting with the idea that MIA acts as a tumour suppressor. To investigate the role of MIA in vivo, we have therefore generated a panel of stably transfected B16 cell clones secreting different amounts of MIA. The capacity of these cell clones to form lung metastases in syngeneic C57Bl6 mice was strictly correlated to the level of MIA secretion, but the clones did not differ with respect to their proliferation in vitro. In summary, we suggest that MIA plays a causal role in promoting the metastasis of malignant melanomas, involving inhibition of tumour cell attachment to extracellular matrix molecules within their local milieu.