For example, the hyaluronan -specific receptor, CD44, which plays an important role in adhesion, has been shown to be involved in CAM-DR through interactions with its ligand HA. Several studies have revealed that CD44s is highly expressed in situ and metastatic ovarian cancers and that CD44 expression is correlated with malignant behaviors of ovarian cancer cells, such as adhesion, invasion, and metastasis. CD44 is modified posttranslationally by glycosylation, which has been shown to influence CD44-mediated CAM-DR. In our preliminary studies, we have found that, although CD44 mRNA levels were similar in a1,2-fucosyltransferase transfected ovarian cancer cells and the parent cells, CD44 protein expression levels were significantly higher in the RMG-1-H cells. In addition, we found that the di-fucosylated Lewis y antigen was a part of the composition of CD44 and that increased expression of this antigen correlated with increased CD44-mediated ovarian cell adhesion and migration. Increased expression of Lewis y antigen and CD44 in RMG-1-H cells was associated with increased resistance to chemotherapeutic drugs, including 5-fluorouracil, carboplatin and paclitaxel. Although the effects of alternative splicing and post-translational glycosylation of CD44 on its interaction with HA have been widely studied in recent years, few reports have described the effects of alterations in fucosylation on CD44-dependent CAM-DR of ovarian cancer cells. Therefore, to address this question, in the present study, we have quantified ovarian cancer drug resistance and expression of Lewis y antigen and CD44 in tissues from ovarian cancer patients. We then used these data to investigate correlations between expression of Lewis y antigen and CD44 and chemotherapeutic resistance, in addition to assess the clinical significance of these correlations. Chemotherapy plays an important role in the management of epithelial ovarian cancer, but acquired resistance to chemotherapy strongly affects therapeutic efficacy and patient survival. CAM-DR is a complicated process involving interactions between adhesion molecules and their associated receptors. One such cell adhesion receptor is CD44, a widely-distributed transmembrane cell surface glycoprotein. CD44 has a complicated and variable structure due to alternative splicing at the transcriptional level and multiple post translational modifications. CD44 is the major HA receptor, and interaction with HA is involved in tumor cell adhesion and migration. Binding of CD44 to HA is regulated by multiple factors, of which glycosylation or glycosaminoglycan modification is the most significant. The molecular weight of unmodified CD44 is 37 kDa, but post-translationally modified CD44 ranges from 85 to 95 kDa. Glycosylation is essential for the CD44-HA interaction, and different oligosaccharide modifications have different effects on CD44 function. Our preliminary studies have shown that di-fucosylated Lewis y antigen is a part of the composition of CD44 and increased levels of Lewis y antigen are associated with increased CD44-mediated ovarian cell adhesion and migration. We also found that cell lines that highly express Lewis y antigen and CD44 exhibit increased resistance to chemotherapeutic drugs, such as carboplatin and paclitaxel. Based on our preliminary studies, we initiated the present study to investigate the correlation between expression of CD44.
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