Cytokine control of cell motility: modulation and mediation by the extracellular matrix

Cytokines are multifunctional regulators of cell behaviour affecting such diverse activities as cell proliferation, gene expression and motility. Matrix macromolecules influence a similarly wide range of cell functions. A review of the available literature suggests that cytokines may affect cell motility by (a) directly influencing the motility apparatus, and (b) indirectly as a consequence of the altered expression of genes coding for matrix macromolecules, their respective cell surface receptors and matrix degrading enzymes and their inhibitors. Conversely, the composition and supramolecular organisation of the matrix plays a central role in defining cellular response to potentially multifunctional cytokines. Such complex and reciprocal interactions between cytokines and the matrix elicit both positive and negative reiterative feedback loops which must be taken into account when interpreting the results of migration assays in vitro and extrapolating them to in vivo processes.