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Vol. 10, Issue 10, 3067-3079, October 1999
2
1 but Not CD44 Mediates MV3 Melanoma
Cell Migration and Matrix Reorganization within Three-dimensional
Hyaluronan-containing Collagen Matrices
*Cell Migration Laboratory, Department of Dermatology, University
of Würzburg, 97080 Würzburg, Germany; and
Haptokinetic cell migration across surfaces is mediated by adhesion
receptors including Institute of Immunology, University of Witten/Herdecke,
58448 Witten, Germany
1 integrins and CD44 providing adhesion to extracellular matrix (ECM) ligands such as collagen and hyaluronan (HA), respectively. Little is known, however, about how such different receptor systems synergize for cell migration through
three-dimensionally (3-D) interconnected ECM ligands. In highly
motile human MV3 melanoma cells, both 1 integrins and CD44
are abundantly expressed, support migration across collagen and HA,
respectively, and are deposited upon migration, whereas only 1
integrins but not CD44 redistribute to focal adhesions. In 3-D
collagen lattices in the presence or absence of HA and cross-linking
chondroitin sulfate, MV3 cell migration and associated functions such
as polarization and matrix reorganization were blocked by anti-1 and
anti-
2 integrin mAbs, whereas mAbs blocking CD44, 3,
5, 6, or v integrins showed no effect. With use of
highly sensitive time-lapse videomicroscopy and computer-assisted cell
tracking techniques, promigratory functions of CD44 were excluded. 1)
Addition of HA did not increase the migratory cell population or its
migration velocity, 2) blocking of the HA-binding Hermes-1 epitope did
not affect migration, and 3) impaired migration after blocking or
activation of 1 integrins was not restored via CD44. Because
21-mediated migration was neither synergized nor replaced by
CD44-HA interactions, we conclude that the biophysical properties of
3-D multicomponent ECM impose more restricted molecular functions of
adhesion receptors, thereby differing from haptokinetic migration
across surfaces.
Online version of this article
contains video material. Online version available at
www.molbiolcell.org.
Corresponding author. E-mail address:
peter.fr{at}mail.uni-wuerzburg.de.
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