The Clinical Significance Of Costimulatory Molecules B7-H1 And B7-H3 In Breast Cancer And The Effects On Biological Behavior Of Breast Tumor Cells

PartⅠThe expression and clinical significance of costimulatory molecule B7-H1 and B7-H3 in human breast cancerObject:To investigate the costimulatory molecule B7-H1 and B7-H3 expression in human breast cancer and to analyze the clinical significanceMethods:With the collection of 59 cases of breast cancer tissus from the surgery with the detailed clinical parameters, using IHC assay to detect the B7-H1 and B7-H3 expression. The clinical significances were figured by statistic software.Resuls:①The results indicated that B7-H1 and B7-H3 were overexpressed in breast cancer cells, in cytoplasm and membrane. B7-H1 was expressed in 47.45% of cases and B7-H3 in 57.62% of cases.②The B7-H1 expression was positively correlated to B7-H3 expression in breast cancer tissues.③The statistic analysis showed that B7-H1 expression was related to Her-2/neu expression but unrelated to other clinical parameters.B7-H3 expression was related to patients'tumor stage but unrelated to other factors.④Both B7-H1 and B7-H3 expression show no relevance to the T cell infiltrating in tumor rissues.⑤The survival analysis showed that B7-H3 expression was negatively correlated to patients'survival time but B7-H1; combination of B7-H1 and B7-H3 expression was significantly correlated to the survival time , patient with B7-H1 and B7-H3 double positive tissue showed the shortest survival time,while the double negative patient show the longest survival time.Conclusion:These data indicated that the co-expression of B7-H1 and B7-H3 were involved in the progression of breast cancer, these two molecules'expression was positively related and the combination of them is of significant clinical value for the diagnosis and prognosis of breast cancer. PartⅡThe effect of B7-H1 and B7-H3 on the biological behavior on breast tumor cellsObject:To explore the influence and mechanism of B7-H1 and B7-H3 signals in breast cancer cell .Methods:MDA-MB-231with B7-H1 and B7-H3 expression and MDA-MB-435 with B7-H3 expression were adopted in the study, B7-H1gene transfected M435 cell was constructed by molecule biologic means, cell number counting and FACs analysis were used to analyze the tumor cell proliferation and cell cycle, and the Annexin-Ⅴ-PI staining was used to analyze the apoptosis cells.Results :①The further study showed that, B7-H1 gene transfection could remarkably promote the proliferation of M435 cell (B7-H1+B7-H3+), as well as M231cell (B7-H1+B7-H3+), comparing to mock-M435cell (B7-H3+).②The cell cycle analysis showed that the S-phase fraction of M435/B7-H1 cell and M231 cell are higer than M435/mock cell.③Using Paclitaxel to induce the apoptosis of breast tumor cells, and the results showed that the apoptosis rate of M435/mock was 18.7%, while the apoptosis rate of M435/B7-H1 and M231 were 9.6% and 5.8%.Conlcusion: This part showed that the co-effect of B7-H1 signal and B7-H3 signal could enhance the breast cell proliferation. And the the co-effect of B7-H1 signal and B7-H3 signal could help the tumor cells survive from the apoptosis induce by chemotherapeutics.Taken together, negative costimulatory molecules B7-H1 and B7-H3 were over-expressed in tumor cells, and played important roles in tumor genesis and progression. The co-effect of B7-H1 signal and B7-H3 signal could enhance the tumor cell proliferation and ability to resist apoptosis induced by chemotherapeutics. The investigation of these two molecules was of significant clinical diagnosis and prognosis value to breast cancer, and could offer new backgrounds for the design of molecule target therapy of breat cancer.