Publication: Are hyaluronan receptors involved in three-dimensional cell migration.
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Date
2000
Authors
Nehls, V. ; Hayen, W.
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Publisher
Murcia : F. Hernández
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DOI
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info:eu-repo/semantics/article
Description
Abstract
Hyaluronan (HA), an unbranched polysaccharide
consisting of repeated glucuronic acid/Nacetylglucosamine
disaccharide units, is ubiquitously
present in the extracellular matrix of many tissues (for a
more comprehensive review see: Fraser et al., 1997).
Increased amounts of hyaluronan are produced by solid
tumors and tumor-associated fibroblasts, and tumorinduced
HA is correlated with poor prognosis. HA is
well known to stimulate the migration of a large variety
of cell types. Stimulation of cell migration by HA has
been explained by different mechanisms. HA was shown
to specifically bind to cell surface receptors, and
inhibition of HA-receptor function was demonstrated to
decrease cell migration and tumor growth. On the other
hand, HA as a large hydrophilic molecule is also known
to modulate the extracellular packing of collagen and
fibrin, leading to increased fiber size and porosity of
extracellular substrates. Hence a modified matrix
architecture might similarly account for increased
locomotion of cells. In this review, we attempted to
summarize the available data on HA-induced cell
migration, with particular emphasis on the role of HA
receptors in three-dimensional cell migration. Although
the HA receptor CD44 has been shown to mediate
migration of cells over two-dimensional hyaluronancoated
surfaces in vitro, there is only little evidence that
HA-binding to CD44 or other HA receptors has major
impact on the locomotion of cells through threedimensional
matrices in vivo. We showed recently that
the promigratory effect of HA in fibrin gels is largely
due to HA-mediated modulation of fibrin
polymerization. By increasing the porosity of fibrin gels,
HA strongly accelerates cell migration. The porosity of
matrices therefore appears as an important and probably
underestimated determinant of cell migration and tumor
spread.
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