CXCR7 expression is associated with disease-free and disease-specific survival in cervical cancer patients

Background:The CXC chemokine receptor (CXCR)7 is involved in tumour development and metastases formation. The aim of the present study was to determine protein expression of CXCR7, its putative co-receptors epidermal growth factor receptor (EGFR) and CXCR4, its predominant ligand CXCL12, their co-dependency and their association with survival in cervical cancer patients.Methods:CXC chemokine receptor 7, EGFR, CXCR4 and CXCL12 expression were determined immunohistochemically in 103 paraffin-embedded, cervical cancers. Subsequently, associations with patient characteristics were assessed and survival analyses were performed.Results:CXC chemokine receptor 7 was expressed by 43% of tumour specimens, in a large majority of cases together with either EGFR or CXCR4 (double positive), or both (triple positive). The CXCR7 expression was associated with tumour size (P=0.013), lymph node metastasis (P=0.001) and EGFR expression (P=0.009). CXC chemokine receptor 7 was independently associated with disease-free survival (hazard ratio (HR)=4.3, 95% confidence intervals (CI) 1.7-11.0, P=0.002), and strongly associated with disease-specific survival (HR=3.9, 95% CI 1.5-10.2, P=0.005).Conclusion:CXC chemokine receptor 7 expression predicts poor disease-free and disease-specific survival in cervical cancer patients, and might be a promising new therapeutic marker. In a large majority of cases, CXCR7 is co-expressed with CXCR4 and/or EGFR, supporting the hypothesis that these receptors assist in CXCR7 signal transduction.Cervix cance

The second extracellular loop: a damper for G protein–coupled receptors?

International audienc

Chemokine receptor oligomerization to tweak chemotactic responses

Chemokine receptors guide cell migration by responding to local chemokine gradients during immune surveillance and inflammation. Similar to other G protein-coupled receptors, chemokine receptors can form oligomeric complexes that might have distinct pharmacological and biochemical properties as compared to their individual constituents. The majority of evidence for chemokine receptor oligomers came from transfected cells using tagged receptors to monitor their close proximity or physical association. However, translation of these observations to (patho)-physiological consequences is puzzling for the majority of chemokine receptor oligomers due to experimental limitations and challenges to distinguish oligomer- from downstream signaling-mediated crosstalk. Recent methodological advances allow in situ validation of chemokine receptor oligomers in native cells, disruption of oligomers, and detection of oligomer-mediated signaling. Chemokine receptor oligomerization modulates cell migration in (patho)-physiology and consequently offers novel therapeutic targets

Immune regulation by atypical chemokine receptors

Chemokines have fundamental roles in regulating immune and inflammatory responses, primarily through their control of leukocyte migration and localization. The biological functions of chemokines are typically mediated by signalling through G protein-coupled chemokine receptors, but chemokines are also bound by a small family of atypical chemokine receptors (ACKRs), the members of which are unified by their inability to initiate classical signalling pathways after ligand binding. These ACKRs are emerging as crucial regulatory components of chemokine networks in a wide range of developmental, physiological and pathological contexts. In this Review, we discuss the biochemical and immunological properties of ACKRs and the potential unifying themes in this family, and we highlight recent studies that identify novel roles for these molecules in development, homeostasis, inflammatory disease, infection and cancer