Hyaluronan Binding by Cell Surface Cd44

Lesley, Jayne; English, Nicole M.; Hascall, Vincent C.; Tammi, Markku; Hyman, Robert

doi:10.1533/9781845693121.341

Cited by 134 publications

(225 citation statements)

References 22 publications

Supporting

Mentioning

215

Contrasting

Unclassified

Order By: Relevance

“…HA 6 do not mediate or disrupt proteoglycan aggregate formation (Hardingham and Muir 1973;Hascall and Heinegard 1974) but, binding of HA 6 to cell surface hyaluronan receptors does compete with binding by large molecular weight hyaluronan (Underhill and Toole 1979;Nemec et al 1987;Lesley et al 2000). The ability of the HA 6 to "disengage" chondrocytes from their matrix in embryonic tibial cartilaginous anlagen (Maleski and Knudson 1996) showed that a chondrocyte in cartilage tissue is "engaged" with its ECM via hyaluronan-hyaluronan receptor interactions.…”

Section: Discussionmentioning

confidence: 99%

Latrunculin and Cytochalasin Decrease Chondrocyte Matrix Retention

Nofal

Knudson

2002

J Histochem Cytochem.

View full text Add to dashboard Cite

S U M M A R YThe proteoglycan-rich extracellular matrix (ECM) directly associated with the cells of articular cartilage is anchored to the chondrocyte plasma membrane via interaction with the hyaluronan receptor CD44. The cytoplasmic tail of CD44 interacts with the cortical cytoskeleton. The objective of this study was to determine the role of the actin cytoskeleton in CD44-mediated matrix assembly by chondrocytes and cartilage matrix retention and homeostasis. Adult bovine articular cartilage tissue slices and isolated chondrocytes were treated with latrunculin or cytochalasin. Tissues were processed for histology and chondrocytes were examined for CD44 expression and pericellular matrix assembly. Treatments that disrupt the actin cytoskeleton reduced chondrocyte pericellular matrix assembly and the retention of proteoglycan within cartilage explants. There was enhanced detection of a neoepitope resulting from proteolysis of aggrecan. Cytoskeletal disruption did not reduce CD44 expression, as monitored by flow cytometry, but detergent extraction of CD44 was enhanced and hyaluronan binding was decreased . Thus, disruption of the cytoskeleton reduces the anchorage of CD44 in the chondrocyte membrane and the capacity of CD44 to bind its ligand. The results suggest that cytoskeletal disruption within cartilage uncouples chondrocytes from the matrix, resulting in altered metabolism and deleterious changes in matrix structure.

show abstract

Section: Discussionmentioning

confidence: 99%

Latrunculin and Cytochalasin Decrease Chondrocyte Matrix Retention

Nofal

Knudson

2002

J Histochem Cytochem.

View full text Add to dashboard Cite

show abstract

“…Oligomers of hyaluronan compete for binding of polymeric hyaluronan to cell-surface receptors, resulting in low-affinity binding 21,22 and attenuation of hyaluronaninduced signaling. 23 Thus we tested whether hyaluronan oligomers inhibit glioma cell invasion of reconstituted basement membrane gels.…”

Section: Hyaluronan Oligomers Inhibit Glioma Cell Invasionmentioning

confidence: 99%

“…The first is addition of hyaluronan oligomers that competitively displace endogenous polymer from its receptors. This leads to low-affinity, monovalent binding rather than high-affinity, polyvalent binding 21,22 and thus to attenuated signaling. 23 The second approach is overexpression of soluble hyaluronan-binding proteins (HABPs) that compete with endogenous receptors by binding endogenous hyaluronan.…”

mentioning

confidence: 99%

Perturbation of Hyaluronan Interactions Inhibits Malignant Properties of Glioma Cells

Ward

Huang

Guo

et al. 2003

The American Journal of Pathology

View full text Add to dashboard Cite

Malignant progression of gliomas is characterized by acquisition of inappropriate growth and invasive properties. In vitro, these malignant properties are reflected in, and measured by, the ability to grow in an anchorage-independent manner and to invade artificial extracellular matrices. The results of numerous studies have suggested that the extracellular and pericellular matrix polysaccharide, hyaluronan, plays an important role in these attributes of malignant cancer cells. However, with respect to glioma cells, most studies have addressed the effect of exogenously added hyaluronan rather than the function of endogenous tumor cell-associated hyaluronan. In this study we manipulate hyaluronan-glioma cell interactions by two methods. The first is administration of small hyaluronan oligosaccharides that compete for endogenous hyaluronan polymer interactions, resulting in attenuation of hyaluronan-induced signaling. The second is overexpression of soluble hyaluronanbinding proteins that act as a competitive sink for interaction with endogenous hyaluronan, again leading to attenuated signaling. We find that both treatments inhibit anchorage-independent growth, as measured by colony formation in soft agar, and invasiveness, as measured by penetration of reconstituted basement membrane matrices. Based on our findings, we conclude that endogenous hyaluronan interactions are essential for these two fundamental malignant properties of glioma cells. Malignant forms of glioblastoma rarely metastasize to distant sites but they are highly proliferative and invasive tumors that destroy normal brain structure and result in high morbidity. As with many types of cancers, up-regulation of growth factor pathways and loss of tumor suppressors have been implicated in glioma development but the mechanisms underlying progression of gliomas to malignancy are by no means established. 1 It has become increasingly apparent that cooperation between signaling pathways induced by growth factors and cytokines and those induced by cell-cell and cell-extracellular matrix interactions are central to regulation of cell behavior. Recent work has highlighted the importance of altered cell-matrix interactions in the acquisition of malignant characteristics. [2][3][4] Hyaluronan is a very large, negatively charged polysaccharide composed of repeating units of glucuronic acid and N-acetylglucosamine. It is ubiquitously associated with extracellular and pericellular matrices but is especially enriched around proliferating and migrating cells. 5 Interactions of hyaluronan with a variety of cell-surface receptors activate intracellular signaling pathways that regulate various aspects of cell behavior 6 and, in tumor cells, promote malignant characteristics. [7][8][9] Several studies have provided evidence that hyaluronan-cell interactions may play a role in glioma invasiveness. For example, addition of exogenous hyaluronan enhances glioma cell migration and invasion in vitro, and this effect is blocked by antibodies or anti-sense oligonucleotides to C...

show abstract

“…For example, recent structural studies show that in the case of CD44, N-and C-terminal sequences flanking the Link module are required to form a folded and functionally active domain (27). Although TSG-6 binds HA with high affinity (28), the binding between CD44 and HA is much weaker (31,32) and seems to depend on multivalent interactions (33)(34)(35). Therefore, extensive occupancy of HA with TSG-6 might be expected to inhibit its interaction with CD44 by reducing the number of sites available for binding.…”

mentioning

confidence: 99%

TSG-6 Modulates the Interaction between Hyaluronan and Cell Surface CD44

Lesley

Gál

Mahoney

et al. 2004

Journal of Biological Chemistry

Self Cite

160

203

View full text Add to dashboard Cite

Interactions between CD44 and hyaluronan are implicated in the primary adhesion of lymphocytes to endothelium at inflammatory locations. Here we show that preincubation of hyaluronan with full-length recombinant TSG-6 or its Link module domain (Link_TSG6) enhances or induces the binding of hyaluronan to cell surface CD44 on constitutive and inducible cell backgrounds, respectively. These effects are blocked by CD44-specific antibodies and are absent in CD44-negative cells. Enhancement of CD44-mediated interactions of lymphoid cells with hyaluronan by TSG-6 proteins was seen under conditions of flow at shear forces that occur in post-capillary venules. Increases in the number of rolling cells were observed on substrates comprising TSG-6-hyaluronan complexes as compared with a substrate containing hyaluronan alone. In ligand competition experiments, cell surface-bound TSG-6-hyaluronan complexes were more potent than hyaluronan alone in inhibiting cell adhesion to immobilized hyaluronan. Link_TSG6 mutants with impaired hyaluronan binding function had a reduced ability to modulate ligand binding by cell surface CD44. However, some mutants that exhibited close to wild-type hyaluronan binding were found to have either reduced or increased activity, suggesting that some amino acid residues outside of the hyaluronan binding site might be involved in protein self-association, potentially leading to the formation of cross-linked hyaluronan fibers. In turn, cross-linked hyaluronan could increase the binding avidity of CD44 by inducing receptor clustering. The ability of TSG-6 to modulate the interaction of hyaluronan with CD44 has important implications for CD44-mediated cell activity at sites of inflammation, where TSG-6 is expressed.

show abstract

Hyaluronan Binding by Cell Surface Cd44

Cited by 134 publications

References 22 publications

Latrunculin and Cytochalasin Decrease Chondrocyte Matrix Retention

Latrunculin and Cytochalasin Decrease Chondrocyte Matrix Retention

Perturbation of Hyaluronan Interactions Inhibits Malignant Properties of Glioma Cells

TSG-6 Modulates the Interaction between Hyaluronan and Cell Surface CD44

Contact Info

Product

Resources

About