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Collective Cell Movement in Primary Melanoma Explants

Plasticity of Cell-Cell Interaction, ß1-Integrin Function, and Migration Strategies^{1 ,,2}

Department of Dermatology, University of Würzburg, 97080 Würzburg, Germany

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 ß1 integrins, as shown by preferential ß1-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-ß1-integrin antibody. Interference with ß1-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 ß1-integrin-independent "amoeboid" crawling and dissemination. The conversion from ß1-integrin-dependent collective movement to ß1-integrin-independent single-cell motility suggests efficient cellular and molecular plasticity in tumor cell migration strategies.

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