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The Variation of Hyaluronic Acid in Breast Cancer and Its Effect on Tight Junction ZO-1 and Proliferation of Lymphatic Endothelial Cells
Yu Mengsi, Liu Yiwen, He Yiqing, Yang Cuixia, Du Yan, Wu Man, Zhang Guoliang, Gao Feng*
Department of Central Laboratory, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai 200233, China
Abstract: This study aimed to investigate the change of hyaluronic acid in breast cancer and further to explore its effect on tight junction ZO-1 distribution and proliferation of lymphatic endothelial cells. Immunohistochemistry and enzyme linked immunosorbent assay were performed to test the expression of hyaluronic acid and serum concentration of hyaluronidase in benign breast disease and breast cancer， normal person and breast cancer， respectively. Immunofluorescence， permeability of sodium fluorescein， MTT and Western blot were applied to investigate the effects of HA and oHA on ZO-1 distribution， permeability of lymphatic endothelial cell monolayers， cell proliferation and the protein expression levels of ROCK1/RhoA. The results showed that the expressions of hyaluronic acid and hyaluronidase in breast cancer were higher than those of benign breast disease and normal person (P<0.01)， respectively. Hyaluronic acid elevated with hyaluronidase in breast cancer， suggesting that the metabolism of HA was more activity. HA strengthened ZO-1 distribution on the cell membrane and unchanged the protein expression levels of ROCK1/RhoA. On the contrary， oHA induced ZO-1 distributed from cell membrane to cytoplasm， leading to disrupting the junction between cells， formed the intercellular space， stimulated permeability of cell monolayers， increased the protein expression levels of ROCK1/RhoA， and promoted proliferation of lymphatic endothelial cells (P<0.01). This study indicated that oHA might play an important role in lymphatic morphogenesis and lymphatic endothelial cell proliferation of breast cancer.
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