Collective cell movement in primary melanoma explants: Plasticity of cell-cell interaction, β1-integrin function, and migration strategies

Collective cell movement represents an efficient dissemination strategy in neoplastic epithelial and mesenchymal cancer. In primary melanoma explants cultured in three-dimensional collagen lattices, invasive migration of multicellular clusters was dependent on the function of β1 integrins, as shown by preferential β1-integrin expression and clustering in a subset of promigratory cells at the leading edge ("guiding cells") and the abrogation of multicellular migration by adhesion-perturbing anti-β1-integrin antibody. Interference with β1-integrin function induced complex changes in cluster polarity and cohesion, including development of two or several opposing leading edges, cluster disruption, and the detachment of individual cells followed by β1-integrin-independent "amoeboid" crawling and dissemination. The conversion from β1-integrin-dependent collective movement to β1-integrin-independent single-cell motility suggests efficient cellular and molecular plasticity in tumor cell migration strategies.