We compared the expression of SDF-1 and CXCR4 in 103 cases of breast cancer containing IMPC components with a control group of 96 cases of invasive ductal carcinoma (IDC), not otherwise specified type by immunohistochemistry and chemical in situ hybridization (CISH).
Recent reports indicate that breast cancer cells lacking expression of CXCL12 but exhibiting CXCR4 can metastasize to target organs that secrete CXCL12.
CXCR4 was more expressed in PT than in metastases (p = 0.0067), whereas CXCL12 was highly expressed in metastatic lesions located in liver and lung (p < 0.0001), as reported for human breast cancer.
Increased expression of chemokines like CXCL12 and dysregulated signaling intermediates such as Notch in patients with solid tumors (e.g., breast cancer) is associated with brain metastasis.
However, except for CXCR4/CXCL12, little is known about the relation between tumour-related chemokine expression and the development and progression of solid tumours like breast cancer.
The stromal fibroblasts isolated from breast cancer tissues showed CAF characteristics with high expression levels of α-smooth muscle actin and SDF1/CXCL12.
On subgroup analysis by cancer type, high CXCL12 expression was associated with reduced overall survival in patients with oesophagogastric (HR 2.08; 95% CI: 1.31-3.33, P=0.002), pancreatic (HR 1.54; 95% CI: 1.21-1.97, P=0.0005) and lung cancer (HR 1.37; 95% CI: 1.08-1.75, P=0.01), whereas in breast cancer patients high CXCL12 expression conferred an overall survival advantage (HR 0.5; 95% CI: 0.38-0.66, P<0.00001).
The rate of breast cancer-specific mortality was much higher in patients with both high p-CXCR4 expression and low plasma SDF-1 levels (HR, 5.96; P < 0.001) than either low plasma SDF-1 (HR, 3.59; P = 0.01) or high p-CXCR4 expression (HR, 3.83; P = 0.005) alone.
High expression of stromal CXCL12 in large cohort of breast cancer patients was directly correlated to blood vessel density and inversely correlated to recurrence and overall patient survival.
Our findings demonstrated that allele A is associated with low expression of CXCL12 in the peripheral blood from ER-positive breast cancer patients, which suggests implications on breast cancer clinical outcome.
Recently, it was reported that the overexpression of stromal cell-derived factor-1 (SDF-1) has great value in human breast cancer diagnosis, suggesting that diagnostic tools and therapies targeting the SDF-1 ligand can improve the clinical outcome.
Flow cytometry, western blot analysis and immunoprecipitation were used to study activation of STAT3 by CXCL12-CXCR4 signaling in human breast cancer cell lines.
The expression levels of CXCR4 and CXCR7 in breast cancer tissues were significantly higher than that in adjacent normal tissues (P=0.022 and P<0.001, respectively), while the expression level of CXCL12 in breast cancer tissues did not differ from that in adjacent normal tissues (P=0.156).
In this study, we found that breast cancer cells exposed to sustained HRG treatment show markedly enhanced Rac1 activation and migratory activity in response to the CXCR4 ligand SDF-1/CXCL12, effects mediated by P-Rex1, a Rac-guanine nucleotide exchange factor (GEF) aberrantly expressed in breast cancer.
Furthermore, higher CXCL12/SDF1 protein expression was associated with positive ER status (OR, 1.92; 95% CI, 1.08-3.45; P = .03), negative HER2 status (OR, 2.64; 95% CI, 1.06-6.59; P = .04), and small tumor size (OR, 2.49; 95% CI, 1.47-4.22; P = .0007) in breast cancer, respectively.
While CXCR4 was consistently detected, expression of CXCL12 characteristic of human mammary epithelium was silenced by promoter hypermethylation in breast cancer cell lines and primary mammary tumors.
LRP6N might be a promising diagnostic marker for the early detection of breast cancer metastasis as well as an inhibitor of SDF-1/CXCR4-induced breast cancer metastasis.
Although SDF-1 and its receptor have been strongly indicated in the progression of various cancers including breast cancer, little is known with regard to the role of other SDFs in malignant conditions including breast cancer.