Disease relevance of CD44

• We previously found that overexpression of CD44 inhibited tumor growth of mouse fibrosarcoma cells in mice [1].

High impact information on CD44

• An anti-CD44 antibody induces a rapid loss of CD44 from both leukocytes and synovial cells and displays an inhibitory effect on cell-extracellular matrix interactions in the synovium [2].
• CD44 is overexpressed by synovial cells and leukocytes, and hyaluronan is overproduced in the rheumatoid synovium and in other inflammatory sites [2].
• A ubiquitous cell adhesion receptor, CD44, preferentially binds hyaluronan, a polysaccharide macromolecule that is present in most extracellular matrices [2].
• CD44 is a glycoprotein that participates in adhesion of lymphocytes to high endothelial cells of lymph organs and likely functions in other intercellular adhesions as well [3].
• This was accompanied by altered serum levels of HA, reduced expression of L-selectin, and a delayed entry of intravenously injected CD44-deficient donor lymphocytes into the arthritic joints of recipient mice [4].

Biological context of CD44

• Mainstream smoke solutions, which produce a phenotype similar to that seen with anti-tenascin and anti-CD44, inhibited expression of CD44 mRNA and increased tenascin mRNA expression [5].
• CONCLUSION: While CD44 is not essential for morphogenesis and autoimmunity, this cell surface receptor seems to play an important role in the development of arthritis, most likely by directing leukocyte traffic to the site of inflammation [4].
• We have taken cells from the surface of recently cavitated joints and subjected them to a brief period of dynamic mechanical strain (3800 microE for 10 min) and measured changes in HA synthesis/release, CD44 expression and HA synthase gene expression [6].
• We have previously demonstrated that the large glycosaminoglycan hyaluronan (HA), in association with its principal cell surface receptor CD44, plays a major role during the morphogenesis of chick joints [6].
• Increased phosphorylation of the CD44 receptor was also observed [7].

Anatomical context of CD44

• This functional assay indicates a role for a CD44 receptor in matrix retention by chick chondrocytes [8].
• Trunk neural crest cells did not express CD44 [9].
• Expression of CD44 during early development of the chick embryo [9].
• At the 18-20 somite stage, CD44 expressing cells were also localized in the caudal region of the embryo, in the mesoderm of the remaining primitive streak and in the caudal ectoderm and above the secondary neural tube during the process of cavitation [9].
• Treatment of CAMs on day 5 of development with antibodies to CD44 or tenascin, but not to other matrix molecules, inhibited CAM growth and affected various aspects of blood vessel development including normal growth and branching of vessels, migration of vessels, and formation and differentiation of the capillary plexus [5].

Associations of CD44 with chemical compounds

• Temporal expression of CD44 during embryonic chick limb development and modulation of its expression with retinoic acid [8].
• Together these data show that tenascin and CD44 play critical roles in early growth and vascular development of the CAM and support the idea that 3-ethylpyridine in mainstream smoke impairs CAM growth and vascular development by targeting expression of tenascin [5].
• The integrin alpha(v)beta(3) and CD44 regulate the actions of osteopontin on osteoclast motility [10].
• The HTC cells are acid phosphatase positive, show expressions of both class I and class II major histocompatibility complex (MHC), CD44, K1, and K55 cell surface antigens, and engulf latex beads, produce nitrite and interleukin-6 on stimulation with bacterial lipopolysaccharide (LPS) [11].
• CD44 is the main cellular receptor for hyaluronic acid (HA) [1].

Physical interactions of CD44

• Our data strongly suggest that osteopontin is an osteoclast autocrine motility factor binding to avb3 and CD44 during stimulation of osteoclast migration [10].

Other interactions of CD44

• Using semi-quantitative RT-PCR, expression of aggrecan, this chick CD44 orthologue and GAPDH mRNA was analyzed [8].
• In addition, the migratory effects of osteopontin on osteoclasts were also mediated through CD44 receptors since blocking antibodies to CD44 blocked stimulation of motility [10].

Analytical, diagnostic and therapeutic context of CD44

• The full-length chick chondrocyte CD44 cDNA was obtained following RT-PCR using RNA derived from tibial chondrocytes from stage 37 chick embryos [8].
• Increased resistance to collagen-induced arthritis in CD44-deficient DBA/1 mice [4].
• Electroporation of in vitro T7-transcribed RNA from the three constructs into IBV helper virus-infected cells resulted in the replication and packaging of CD-58 and CD-61 but not CD-44 RNA [12].
• Southern blot hybridization also showed the presence of a polymorphic variant of Japanese flounder CD3 [13].

References