Regulation of the chemokine receptors CXCR7 and CXCR4 in 3-D culture models of prostate cancer

Regulation of the chemokine receptors CXCR7 and CXCR4 in 3-D culture models of prostate cancer

CXCR7 was recently identified as the second member of the chemokine receptor family to bind stromal derived factor-1α (SDF-1α), a chemokine which is known to influence the establishment of cancer metastasis. Whilst expression of CXCR7 is highly restricted in non-malignant cells, it is widely expressed in many different tumor cell lines. In prostate cancer, a disease known to be highly regulated by the other SDF-1α -binding receptor CXCR4, CXCR7 has been found to regulate cell growth and invasion. In vivo prostate tumor biopsies show a pattern where CXCR7 expression increases with invasive grade, as previously reported for CXCR4. However, there is limited knowledge on the role of CXCR7 and its function in prostate cancer.

In this study, we aim to more thoroughly characterize CXCR7 function across prostate cancer cell lines, in particular its regulation of cell growth and behavior. We will also assess its expression and function in response to its ligands and inhibitors, alongside CXCR4, in order to assess how these receptors are regulated in relation to each other. For this we employ western blotting expression studies, immunocytochemical visualization, and metabolic-based proliferation assays.

Further, we will study the regulation of both CXCR7 and CXCR4 in 3D culture models of prostate cancer cell lines. Our preliminary data from 2D culture suggests that less invasive prostate cancer cell lines express higher levels of CXCR7 than more invasive cell lines, contrary to reports in vivo where CXCR7 expression was seen to increase with invasive grade. We have chosen to assess these aspects in 3D cultures of prostate cancer cell lines to determine whether culturing in 3D permits a phenotype more reflective of what has been reported for CXCR7 expression in prostate cancer in vivo.

Further elucidation of CXCR7 function with respect to CXCR4 will shed light on how these receptors contribute to regulation of the metastatic process in prostate cancer – a process known to be heavily regulated by CXCR4. As CXCR4 has been established as a therapeutic target in prostate cancer, a more detailed knowledge of the CXCR7 receptor with which it shares a partial redundancy may indicate whether combinatorial therapies may be more effective in combating prostate cancer progression.

Abstract #C50.