The role of chemokine receptor 4 and its ligand stromal cell derived factor 1 in breast cancer

Breast tumour cells express the chemokine receptor C-X-C chemokine receptor type 4 (CXCR4) and frequently metastasize to organs with an abundant source of CXCR4 ligand, stromal cell derived factor1 (SDF1). For this reason, CXCR4/SDF1 has garnered much interest as a target for therapeutic intervention. The present study is an attempt to correlate the CXCR4/SDF1 expression patterns with clinicopathological factors, patient survival, and its coexistence and response to 17-β estradiol (E₂) and 4-hydoxytamoxifen (4OHT) in breast cancer cells. Immunohistochemistry and Reverse Transcriptase-Polymerase Chain Reaction were performed to assess the protein and gene level expressions of CXCR4 and SDF1 in normal and tumour breast tissue. The effect of E₂ and 4OHT on expression of CXCR4 and SDF1 in breast cancer cells were assessed using RTPCR, Immunofluorescence microscopy and colocalization. The CXCR4 and SDF1 were over expressed and have a significant correlation with each other as well as with histological grade, tumour size and poor survival of patients. The study also showed a modulatory effect of E₂ and 4OHT on the expression and colocalization of CXCR4/SDF1 in breast cancer cells. The correlation of CXCR4/SDF1 with other parameters and modulatory effect of E₂ and 4OHT on the expression and colocalization of CXCR4/SDF1 in breast cancer cells are likely to open up new avenues for the successful management of this malignancy.