| Summary: | 碩士 === 國立陽明大學 === 解剖暨細胞生物學研究所 === 93 === Hyaluronan (HA), a characteristic component of the extracellular matrix and also a linear and nonbranch polysaccharide. It plays an important part in cell-cell adhesion and cell migration. CD44, a surface receptor of HA, plays a major role in cell-cell adhesion, cell-substrate interaction, lymphocyte homing, and tumor metastasis. However,the functional relevance of CD44 to tumor cell metastasis remains unknown. Previous studies have shown that CD44 was highly expresseed in breast tumor cells. Recently, proteolytic cleavages of CD44 have been emerging as key regulatory events for the CD44 undergoes sequential proteolytic cleavages in the ectodomain and intramembranous domain, resulting in the release of CD44 intacellular domain (CD44 ICD) and it’s cleavage plays a important role in tumor cell migration. In this study, we investigated the mechanisms of HA-induced CD44 ICD cleavage using MDA-MB-435s breast cancer cell line. Using Western blot, we found that after HA stimulation, CD44 ICD expression in the cytoplasm was increase. Immunofluorescence staining data also further confirmed that CD44 ICD was translocated into the nucleus. Following by cDNA microarray analysis, the gene expression was also regulated after HA stimulation. We concluded that HA induces CD44 ICD release and the released ICD then translocate into nucleus to regulate gene expression in the breast tumor cells.
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