Autocrine motility factor and the extracellular matrix. I. Coordinate regulation of melanoma cell adhesion, spreading and migration involves focal contact reorganization.

Cellular interactions with the extracellular matrix are complex and are involved in numerous biological processes. These interactions may be modulated by cytokines such as tumor cell autocrine motility factor, a secreted molecule that regulates cellular growth and migration by a receptor-mediated pathway. In this report we provide evidence suggesting that high- and low-metastatic K1735 melanoma cells coordinate their attachment, spreading and migratory responses to autocrine motility factor and the extracellular substratum through alterations in focal adhesion plaque architecture that are dependent on both inherent cellular metastatic phenotype and the composition of the supporting matrix. Thus, since activation of the autocrine motility factor receptor has previously been shown to enhance the experimental metastasis of the high- but not the low-metastatic K1735 cells, differences in melanoma cell malignancy in this system may be due in part to a coordinated interplay between cytokine-mediated responses and extracellular matrix-directed regulation of cellular adhesion, spreading and motility.