CXCR4 has also been found to be a prognostic marker in various types of cancer, including leukemia and breast cancer, and recent evidence has highlighted the role of CXCR4 in prostate cancer.
Chemokine receptor interactions are important modulators of breast cancer metastasis; however, it is now recognized that quantitative surface expression of one important chemokine receptor, CXCR4, may not directly correlate with metastasis and that its functional activity in breast cancer may better inform tumor pathogenicity.
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.
A 21-residue peptide derived from the viral macrophage inflammatory protein II (NT21MP), competes with the ligand of CXC chemokine receptor 4 (CXCR4) and its ligand stromal cell-derived factor-1α, inducing cell apoptosis in breast cancer.
A statistically significant correlation was disclosed between the negative expression of PR receptors and a high expression of CXCR4 in patients with BC.
According to the ability of cancer-associated fibroblasts (CAFs), the most abundant component of breast cancer stroma, to secrete high levels of SDF-1α, BRL reduced migratory promoting activities induced by conditioned media (CM) derived from CAFs and affected CXCR4 downstream signaling pathways activated by CAF-CM.
Adhesion to and migration through a HUVEC monolayer were significantly reduced by lentiviral inhibition of CXCR4 in breast carcinoma cells or treatment of endothelial cells with an anti-SDF-1 neutralizing antibody.
Although NCOA1 is known to promote breast cancer metastasis through working with multiple transcription factors to upregulate the expression of Twist1, ITGA5, CSF-1, SDF1 and CXCR4, the role of NCOA1 in breast tumor angiogenesis has not been investigated.
Androgen Triggers the Pro-Migratory CXCL12/CXCR4 Axis in AR-Positive Breast Cancer Cell Lines: Underlying Mechanism and Possible Implications for the Use of Aromatase Inhibitors in Breast Cancer.
Bioluminescence imaging showed that CXCR7+ breast cancer cells enhanced proliferation of CXCR4+ breast cancer cells in orthotopic tumors and spontaneous metastases.
Chemotaxis mediated by chemokine receptors such as CXCR4 plays a key role in lymphocyte homing and hematopoiesis as well as in breast cancer metastasis.
Chromatin immunoprecipitation experiments confirmed that in ANXA1 overexpressed cells, NF-κB was recruited to CXCR4 promoter without external stimulation, indicating that ANXA1 is critical for the constitutive activation of NF-κB in breast cancer to promote metastasis.
Collectively, our study provided new insights into the function of CXCR4 in breast cancer: it promotes tumor progression as both a protein-coding gene and a non-coding RNA, complicating the mechanism by which oncogenes promote tumor progression.
Collectively, these findings suggest our CXCR4 antagonists have promising clinical utility for HIV or breast cancer therapies as well as being useful probes to examine the link between CXCR4 and apoptosis.
Combination treatment using the CXCR4 antagonist AMD3465 and the IDO1 inhibitor D1MT successfully delayed the progression of breast cancer bone metastases.