Abnormal In Stromal Cells And Signal Pathway Of NF-κB, RKIP And Other Molecules During Breast Cancer Development

Objectives: To investigate the role of the mammary stromal cells (adipocytes, fibroblasts and vascular endothelial cells) during breast cancer development. The activation of NF-kB and its downstream proteins' expression of VEGF-C and VEGFR3 in breast neoplasms and mammary stromal cells were detected. To evaluate the correlation of these specific factors in mammary stroma components with clinicopathogical parameter including lymph node involvement and histological grade(differentiation).Methods: Seventy-one cases of human breast neoplasms including 11 cases of atypical ductal hyperplasia, 14 cases of the high-differentiation( Grade I ), 32 cases of the moderate-differentiation (Grade II) and 14 cases of the low-differentiation( Grade III), in addition, 40 cases of non-neoplastic hyperplasia of the rats induced by DMBA.NF-kB, VEGF-C and VEGFR3 in tumor cells and in the stromal cells including adipocytes, fibroblasts and vascular endothelial cells were examined through immunohistochemical methods to evaluate the correlation of the activation of NF-kB VEGF-C and VEGFR3 in tumor cells and in the stromal cells. Results:1. The activation of NF-kB in breast neoplasm cells positively correlated with lymph node involvement(P<0.05) and histological grade(P<0.05).2. The activation of NF-kB in stromal cells including fibroblasts, adipocytes and endothelial cells positively correlated with lymph node involvement(P<0.05) and histological grade(P<0.05).3. The level of VEGF-C expression in breast cancer cells had no significant correlation with histological grade lymph node involvement(P>0.05) and had positivecorrelation with histological grade (P<0.05).4. The level of VEGF-C expression in stromal cells including fibroblasts, adipocytes and endothelial cells positively correlated with lymph node involvement(P<0.05) and histological grade(P<0.05).5. The level of VEGF-R expression in breast cancer cells had no significant correlation with lymph node involvement(.P>0.05) and histological grade(P>0.05).6. The level of VEGF-R expression in stromal cells including fibroblasts and endothelial cells positively correlated with lymph node involvement(P<0.05) and histological grade(P<0.05). The level of VEGF-R expression in adipocytes had no significant correlation with histological grade (P>0.05) and positively correlated with lymph node involvement(P<0.05)7.. The level of VEGF-C expression in stromal cells including fibroblasts, adipocytes and endothelial cells positively correlated with the activation of NF-kB in stroma.8. The level of VEGF-C expression in stromal cells including fibroblasts, adipocytes and endothelial cells positively correlated with the expression of VEGFR3 in stroma.9. There are some non-neoplastic hyperplasia of the rats induced by DMBA.shown the activation of NF-kBConclusion:1. NF-kB was activated abnormally in part of the total breast cancer cells and its surrounding stromal cells. The activation of NF-kB in tumor cells and stromal cells had positive correlation with lymph node involvement and histological grade. The stromal cells play an important role in breast cancer development.2. The activation of the stromal cells including adipocytes, fibroblasts and vascularendothelial cells enhanced its VEGF-C expression. The high level of VEGF-C in tumor microenviroment stimulates stromal cells to express VEGFR3 and lymphogenesis, enhance tumor invasion. Meanwhile, the activation of NF-kB and VEGF-C expression in stromal cells had positive correlation with breast cancer development.