caa a22 4500 475844858 CHVBK 20180406123911.0 cr unu---uuuuu 170329e20000101xx s 000 0 eng 10.1007/s000180050498 doi (NATIONALLICENCE)springer-10.1007/s000180050498 The biology of cell locomotion within three-dimensional extracellular matrix [Elektronische Daten] [P. Friedl, E.-B. Bröcker] Abstract.: Cell migration in three-dimensional (3-D) extracellular matrix (ECM) is not a uniform event but rather comprises a modular spectrum of interdependent biophysical and biochemical cell functions. Haptokinetic cell migration across two-dimensional (2-D) surfaces consists of at least three processes: (i) the protrusion of the leading edge for adhesive cell-substratum interactions is followed by (ii) contraction of the cell body and (iii) detachment of the trailing edge. In cells of flattened morphology migrating slowly across 2-D substrate, contact-dependent clustering of adhesion receptors including integrins results in focal contact and stress fiber formation. While haptokinetic migration is predominantly a function of adhesion and deadhesion events lacking spatial barriers towards the advancing cell body, the biophysics of the tissues require a set of cellular strategies to overcome matrix resistance. Matrix barriers force the cells to adapt their morphology and change shape and/or enzymatically degrade ECM components, either by contact-dependent proteolysis or by protease secretion. In 3-D ECM, in contrast to 2-D substrate, the cell shape is mostly bipolar and the cytoskeletal organization is less stringent, frequently lacking discrete focal contacts and stress fibers. Morphologically large spindle-shaped cells (i.e., fibroblasts, endothelial cells, and many tumor cells) of high integrin expression and strong cytoskeletal contractility utilize integrin-dependent migration strategies that are coupled to the capacity to reorganize ECM. In contrast, a more dynamic ameboid migration type employed by smaller cells expressing low levels of integrins (i.e., T lymphocytes, dendritic cells, some tumor cells) is characterized by largely integrin-independent interaction strategies and flexible morphological adaptation to preformed fiber strands, without structurally changing matrix architecture. In tumor invasion and angiogenesis, migration mechanisms further comprise the migration of entire cell clusters or strands maintaining stringent cell-cell adhesion and communication while migrating. Lastly, cellular interactions, enzyme and cytokine secretion, and tissue remodeling provided by reactive stroma cells i.e. fibroblasts and macrophage contribute to cell migration. In conclusion, depending on the cellular composition and tissue context of migration, diverse cellular and molecular migration strategies can be developed by different cell types. Birkhäuser Verlag Basel,, 2000 Key words. Collagen matrix nationallicence cell migration nationallicence integrins nationallicence CD44 nationallicence matrix metalloproteinases nationallicence attachment nationallicence detachment nationallicence tissue remodeling nationallicence tumor invasion nationallicence antibody blocking nationallicence haptokinetic nationallicence Friedl P. Cell Migration Laboratory, Department of Dermatology, University of Wuerzburg, Josef-Schneider-Strasse 2, D-97080 Wuerzburg (Germany), Fax +49 031 2012700, e-mail: peter.fr@mail.uni-wuerzburg.de, DE aut Bröcker E.-B Cell Migration Laboratory, Department of Dermatology, University of Wuerzburg, Josef-Schneider-Strasse 2, D-97080 Wuerzburg (Germany), Fax +49 031 2012700, e-mail: peter.fr@mail.uni-wuerzburg.de, DE aut https://doi.org/10.1007/s000180050498 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s000180050498 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Friedl P. Cell Migration Laboratory, Department of Dermatology, University of Wuerzburg, Josef-Schneider-Strasse 2, D-97080 Wuerzburg (Germany), Fax +49 031 2012700, e-mail: peter.fr@mail.uni-wuerzburg.de, DE aut NATIONALLICENCE 700 1- Bröcker E.-B Cell Migration Laboratory, Department of Dermatology, University of Wuerzburg, Josef-Schneider-Strasse 2, D-97080 Wuerzburg (Germany), Fax +49 031 2012700, e-mail: peter.fr@mail.uni-wuerzburg.de, DE aut Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer