The Study Of The Relationship Between SDF-1 And CXCR4 In Tumor Growth And Metastasis Of Breast Cancer

Objectives To investigate the expression and prognostic value of stromal cell-derived factor-1(SDF-1)and CXCR4 receptor in human breast cancer tissues and axillary metastatic nodes and CXCR4 in a mouse model of human breast cancer metastasis to implanted human bone by injecting human breast cancer cells into the left cardiac ventricle in severe combined immunodeficient(SCID/berg)female mice.Methods SDF-1 and CXCR4 were detected in 50 breast cancer tissues (group A),26 axillary metastatic nodes(group B)and 10 control group breast tissues(group C)by immunohistochemistry.50 SCID/berg female mice with 4 to 5 week old were randomly divided into experimental(n=30) and control group(n=20).Then the experimental group had human bone implanted into right or left dorsal flanks and was divided into group A,B,C. Animals in Group A,B,C were respectively injected with 1×10~5,1×10~6 human breast cancer stem-like cells,and 1×10~6 parental MDA-MB-231 cells. A positive control group D without implantation of human bone was also injected with 1×10~6 MDA-MB-231 parental cells.A group of negative controls E with implantation of human bone was injected with isotonic sodium chloride.All animals were sacrificed at week 8. Immunohistochemistry and real-time PCR were performed for CXCR4.Results Positive rates of SDF-1 in group A and group C were 90%and 70%respectively(P＞0.05).Positive rates of CXCR4 in group A and group C were 72%and 10%respectively(P＜0.01).Expression of SDF-1 and CXCR4 in breast cancer tissues with axillary lymph node metastasis was higher than that in breast cancer tissues without axillary lymph node metastasis,which was closely associated with axillary lymph node metastasis(P＜0.01).Postitive rate of SDF-1 and CXCR4 in axillary metastatic nodes was high as well as in primary lesion.Bone metastatic morbidity in group B was highest among all groups(77.8%,P=0.048).The expression of CXCR4 in bone metastasis tissues was stronger in group B than that of group C,D(P＜0.05).The real-time PCR showed there the mRNA levels of CXCR4 in bone metastasis tissues of group B were all higher than that of group C and D(8.4-fold,28.4-foldmrespectively)Conclusion Expressions of SDF-1 and CXCR4 may have a close relationship with tumor growth and metastasis of breast cancer.It may be taken as a valuable marker for evaluating prognosis of the patients with breast cancer.