| Summary: | 碩士 === 國立陽明大學 === 藥理學研究所 === 101 === Galectin-4 （gal-4）, a member of galectins family, is composed of a linker peptide and 2 carbohydrate recognition domains at each end, that could bind with β-galactoside. Previous studies have shown that gal-4 plays inhibitory roles on cell proliferation, migration, and Wnt signaling pathway. On the other hand, gal-4 could promote cell apoptosis, and inflammation. Gal-4 is thought as an indicator of differentiation and also a tumor suppressor in colorectal cancer. However, the underlying mechanism is still unknown. According to unpublished clinical data, bladder cancer patients with hypermethylation in gal-4 promoter showed poor prognosis. Furthermore, gal-4 expression became lower when grade and stage got higher, whereas it was not associated with metastasis. In addition, numerous bladder cancer cell lines did not express gal-4. By ectopic-expressed gal-4 in bladder cancer cell line, T24, gal-4 could be found in the conditioned medium. Therefore, this study aims to explore the role of gal-4 in bladder cancer. The present results showed that the morphology was changed in ectopic-expressed gal-4 where it mainly existed in cytosol. To explore the function of gal-4, cell migration ability and drug sensitivity were investigated in cells with or without ectopic expression of gal-4. Results showed that gal-4 could inhibit cell migration, but not invasion; in ectopic-expressed gal-4 cells, the drug sensitivity to gemcitabine and cisplatin were enhanced as compared to those of vector control cells. Furthermore, gal-4 expression would decrease the protein levels of integrin-β3, phospho-cdc42 and phospho-AKT which may associate with reduced cell migration and increased sensitivity to drugs. In addition, recombinant human gal-4 （rh-gal-4） expressed in E.coli was purified using Ni-NTA resin through low pressure liquid chromatography. Addition of rh-gal-4 to cultured medium, rh-gal-4 was found to bind to cell membrane, but has no influence on cell morphology. These results suggested that gal-4 may play a role in enhancing drug-sensitivity and negatively regulating tumor behavior in bladder cancer. The secreted gal-4 may regulate cell signaling or behavior by interaction with cell surface.
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