Upregulation of CXC chemokine receptor 4-CXC chemokine ligand 12 axis ininvasive breast carcinoma: A potent biomarker predicting lymph node metastasis.

Abstract

Breast cancer is considered as a heterogeneous disease, characterized by different biological and phenotypic features which make its diagnosis and treatment challenging. The CXC chemokine receptor 4 (CXCR4) expression was found to be correlated with poor overall survival in invasive breast carcinoma patients. Here, we sought to investigate the expression levels of the CXCR4-CXC chemokine ligand 12 (CXCL12) chemokine axis and their association with clinicopathologic features and lymph node metastasis in invasive breast carcinoma. The expression of the CXCR4-CXCL12 chemokine axis and metastasis-related genes (E-cadherin and matrix metalloproteinase 2 [MMP2]) was measured by quantitative real-time-polymerase chain reaction. The correlation with various clinicopathologic parameters was analyzed. We found upregulation of the CXCR4-CXCL12 chemokine axis in invasive breast carcinoma samples compared with normal adjacent tissues. Moreover, we observed that upregulation of this chemokine axis was correlated with tumor stages and lymph node metastasis of breast tumors. Interestingly, this correlation was affected by the expression of human epidermal growth factor receptor 2/neu. There is also a significant correlation between the expression levels of CXCR4-CXCL12 axis and metastasis-related genes (E-cadherin and MMP2) in tumor samples with advanced stages of metastasis. These results suggest a key role for the CXCR4-CXCL12 chemokine axis in breast cancer progression and highlight the prognostic importance of this chemokine axis for breast cancer survival.