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The development and progression of tumor cells is controlled by their interactions with neighboring host cells and a variety of microenvironmental factors including extracellular matrix (ECM) molecules, growth factors and proteinases. Cell-adhesive ECM proteins are a prerequisite for growth and migration of many types of cells. Their interactions with integrins and other cell surface receptors induce intracellular signaling that regulates the actin cytoskeleton and gene expression. The basement membrane protein laminin-5 is a notable cell adhesion molecule, which promotes cellular adhesion and migration much more efficiently than other ECM proteins. There is accumulating evidence that laminin-5 is involved in tumor growth and progression. With special reference to laminin-5, this article reviews the regulatory mechanisms of cellular adhesion and migration by ECM molecules and their significance in tumor progression. (Cancer Sci 2006; 97: 91 – 98)