A novel chemokine receptor for SDF-1 and I-TAC involved in cell survival, cell adhesion, and tumor development

Abstract

The chemokine stromal cell–derived factor (SDF-1; also known as chemokine ligand 12 [CXCL12]) regulates many essential biological processes, including cardiac and neuronal development, stem cell motility, neovascularization, angiogenesis, apoptosis, and tumorigenesis. It is generally believed that SDF-1 mediates these many disparate processes via a single cell surface receptor known as chemokine receptor 4 (CXCR4). This paper characterizes an alternate receptor, CXCR7, which binds with high affinity to SDF-1 and to a second chemokine, interferon-inducible T cell α chemoattractant (I-TAC; also known as CXCL11). Membrane-associated CXCR7 is expressed on many tumor cell lines, on activated endothelial cells, and on fetal liver cells, but on few other cell types. Unlike many other chemokine receptors, ligand activation of CXCR7 does not cause Ca2+ mobilization or cell migration. However, expression of CXCR7 provides cells with a growth and survival advantage and increased adhesion properties. Consistent with a role for CXCR7 in cell survival and adhesion, a specific, high affinity small molecule antagonist to CXCR7 impedes in vivo tumor growth in animal models, validating this new receptor as a target for development of novel cancer therapeutics.

Chemokines and Cancer Progression: A Qualitative Review on the Role of Stromal Cell-derived Factor 1-alpha and CXCR4 in Endometrial Cancer

“…CXCR7 was identified by Burns et al [17] as a novel receptor for SDF-1alpha; in vitro, the interaction of SDF-1alpha and CXCR7 enhanced growth and adhesion of cells from several different cell lines. Tumor samples and adjacent non-neoplastic tissues were analyzed by reverse transcriptase-polymerase chain reaction (RT-PCR) and IHC for the detection of mRNA and protein, respectively.…”

The SDF-1–CXCR4 signaling pathway: a molecular hub modulating neo-angiogenesis

“…Recently, a new SDF-1 receptor named CXCR7 has been discovered [66,67]. CXCR7 is also expressed on tumor cells and endothelium and regulates tumor growth [67,68].…”

“…Recently, a new SDF-1 receptor named CXCR7 has been discovered [66,67]. CXCR7 is also expressed on tumor cells and endothelium and regulates tumor growth [67,68]. As such, it is conceivable that CXCR4-independent effects of SDF-1 on angiogenesis could potentially be attributed to CXCR7 [69].…”

DNA methylation regulates the expression of CXCL12 in rheumatoid arthritis synovial fibroblasts

“…8 A second receptor for CXCL12, CXCR7 has only most recently been identified and has been implicated in tumor growth and metastasis. [9][10][11] Elevated levels of CXCL12 were found in patients with multiple sclerosis, inflammatory myopathies, spondyloarthropathies and RA. [12][13][14][15][16][17] Levels of CXCL12 in the synovial fluid of RA patients are around 10 times higher than in healthy joints and reach a mean of 750 ng ml À1 .…”