A Role For Sialyl Lewis X In Angiogenesis In Breast Cancer

Objective: SLex, a carbohydrate antigen, is expressed in glycoproteins and glycolipids of tumor cell surface. The expression of SLex correlates with tumor invasion, metastasis and prognosis significantly. Before metastasis of cancer cells in blood circulation, it must adhere to the vascular endothelial cell. Therefore, the adhesion between cancer cells and vascular endothelial cells is an important step for hematogenous metastasis. This adhesion is mediated by SLex expressed in cancer cells and E-selectin expressed in vascular endothelial cells. The Specific combination between SLex and E-selectin, is related not only to tumor invasion and metastasis, but also to angiogenesis in vitro and animal experiments. It has been proven by clinical trials that SLex correlates with breast cancer metastasis and prognosis. But the relation between SLex and breast cancer angiogenesis has not been reported.Angiogenesis is the original veinule or capillary endothelial cell proliferation and migration from the pre-existing site, forming new capillary through gemmation or nongemmation. It is a process from little to more and related to adult diseases. A number of animal experiments proved that tumor angiogenesis plays an important role in the growth and metastasis of tumors. Tumor growth and metastasis are vascular dependent. In early stages of pre-angiogenesis, the tumor is usually very small, and the number of cells is limited. From the beginning of angiogenesis, tumor cells rapid increase. At present, tumor microvessel density is used to evaluate tumor angiogenesis, which is the current standard method.Currently, it is widely held that VEGF is one of the most importantfactors in the induction of tumor angiogenesis. VEGF is correlated with tumor development, metastasis diagnosis, prognosis and recurrence. VEGF level in tumor tissue is correlated with microvessel density.SLex and E-selectin are closely correlated with tumor invasion and metastasis and with tumor neovascularization. VEGF has become the hot of research. Because SLex relates to adhesion, the majority of studies are focused on tumor invasion and metastasis, but the interaction between E-selectin and SLex is overlooked with the effects of angiogenesis. The purpose of this study is to make a preliminary test on whether SLex is associated with MVD in breast cancer, and to lay a foundation for further study of specific signal transduction path.By mean of the immunohistochemical staining for breast cancer specimens, we analyzed the link between SLex expression and microvessel density (MVD), as well as link between SLex expression and VEGF expression to evaluate the SLex's impact on breast cancer angiogenesis.Methods: SLex, MVD, VEGF expression in paraffin sections of 94 cases of breast cancer has been studied with immunohistochemical methods. Using SLex antibody, VEGF antibody, CD34 antibody, MVD is counted.Biological professional image analysis software (imagepro-plus 6.0) is used to analyze SLex staining. VEGF staining intensity is studied with the integrated optical density; Microvessel counting comes from the high-power field image. According to the diameter of the tumor, clinical stage, lymph node metastasis, histological grade, specimens of 94 patients was divided into different groups. First, statistical analyses was used to test the different expression of SLex VEGF, CD34, and then the relationship between MVD and SLex expression, and between VEGF and SLex expression were analyzed to test relevance of SLex expression and angiogenesis.Results: 1, SLex expression, MVD, VEGF expression were closely related to the histological grading of breast cancer, lymph node metastasis and the clinical stage in breast cancer, but not related to the diameter of the tumor. 2, Between SLex low expression group and high expression group, MVD and VEGF were significantly different. 3, SLex expression is significantly correlated with the MVD.Conclusion: 1, SLex expression was significantly correlated with themalignant degree of breast cancer, lymph node metastasis. SLex may be considered as a marker of breast cancer. 2, SLex expression and MVD was significantly correlated in breast cancer. SLex maybe play a role in angiogenesis in breast cancer. 3,. SLex plays a role in breast cancer malignant behavior by mediating adhesion between cancer cells and vascular endothelial cells, enhancing the ability of tumor invasion and metastasis; and more importantly by promoting tumor angiogenesis for hematogenous and lymphatic metastasis.