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 RT-PCR, 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.
1 Division of Cancer Research, 2 Division of Surgical Oncology, 3 Division of Pathology, Regional Cancer Centre, Post Box No. 2417, Medical College P.O, Thiruvananthapuram- 695011, Kerala, India.
Binu Kottakkal
BK
Aravindan
1 Division of Cancer Research, 2 Division of Surgical Oncology, 3 Division of Pathology, Regional Cancer Centre, Post Box No. 2417, Medical College P.O, Thiruvananthapuram- 695011, Kerala, India.
Jem
J
Prabhakar
1 Division of Cancer Research, 2 Division of Surgical Oncology, 3 Division of Pathology, Regional Cancer Centre, Post Box No. 2417, Medical College P.O, Thiruvananthapuram- 695011, Kerala, India.
Thara
T
Somanathan
1 Division of Cancer Research, 2 Division of Surgical Oncology, 3 Division of Pathology, Regional Cancer Centre, Post Box No. 2417, Medical College P.O, Thiruvananthapuram- 695011, Kerala, India.
Lakshmi
L
Subhadra
C-X-C chemokine receptor type 4 (CXCR4); breast cancer; chemokines; stromal cell derived factor1 (SDF1)