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When cells are stimulated to move, for instance during development, wound healing or angiogenesis, they undergo changes in the turnover of their cell-matrix adhesions. This is often accompanied by alterations in the expression profile of integrins-the extracellular matrix receptors that mediate anchorage within these adhesions. Here, we discuss how a shift in expression between two different types of integrins that bind fibronectin can have dramatic consequences for cell-matrix adhesion dynamics and cell motility.

Cell migration is essential in a number of processes, including wound healing, angiogenesis and cancer metastasis. Especially, invasion of cancer cells in the surrounding tissue is a crucial step that requires increased cell motility. Cell migration is a well-orchestrated process that involves the continuous formation and disassembly of matrix adhesions. Those structural anchor points interact with the extra-cellular matrix and also participate in adhesion-dependent signalling. Although these processes are essential for cancer metastasis, little is known about the molecular mechanisms that regulate adhesion dynamics during tumour cell migration. In this review, we provide an overview of recent advanced imaging strategies together with quantitative image analysis that can be implemented to understand the dynamics of matrix adhesions and its molecular components in relation to tumour cell migration. This dynamic cell imaging together with multiparametric image analysis will help in understanding the molecular mechanisms that define cancer cell migration. [ABSTRACT FROM AUTHOR]

Background: Integrins are a family of transmembrane receptors that mediate cell-cell and cell-matrix adhesion. They are involved in stable cell adhesion and migration of cells. In addition, integrin-mediated interactions modulate the response to most, if not all growth factors, cytokines, and other soluble factors. Purpose: In this review, we briefly explain how integrins can affect the multitude of signal transduction cascades in control of survival, proliferation, and differentiation. Subsequently, we primarily focus on targeting integrins α5β1 and αvβ3 in disease and we discuss how antagonists of these integrins, including disintegrins, RGD peptides, small molecules, and function blocking antibodies, may be of therapeutical value either alone or, especially in the treatment of cancer, in combination with existing therapeutical strategies. [ABSTRACT FROM AUTHOR]

Focal adhesions are randomly distributed across the ventral surface or along the edge of epithelial cells. In fibroblasts they orient centripetally and concentrate at a few peripheral sites connecting long F-actin stress fibers, causing a typical elongated, contractile morphology. Extensive remodeling of adhesions in fibroblasts also takes part in fibronectin fibrillogenesis, a process that depends on Rho-mediated contractility and results in the formation of a fibronectin matrix. Our current study shows that all these fibroblast characteristics are controlled by the ability of integrin {alpha}5β1 to bind soluble fibronectin molecules in their compact inactive conformation. The hypervariable region of the ligand-binding I-like domain of integrin {alpha}5β1 supports binding of soluble fibronectin. This supports the distribution of centripetally orientated focal adhesions in distinct peripheral sites, Rho activation and fibronectin fibrillogenesis through a mechanism that does not depend on Syndecan-4. Integrin {alpha}vβ3, even when locked in high affinity conformations for the RGD recognition motif shows no appreciable binding of soluble fibronectin and, consequently, fails to support the typical fibroblast focal adhesion distribution, Rho activity and fibronectin fibrillogenesis in the absence of integrin {alpha}5β1. The ability of {alpha}5β1 integrin to interact with soluble fibronectin may thus drive the cell-matrix adhesion and cytoskeletal organization required for a contractile, fibroblast-like morphology, perhaps explaining why {alpha}5β1 integrin, similarly to fibronectin, is essential for development. [ABSTRACT FROM AUTHOR]