title: CRAM-A indicates IFN-γ-associated inflammatory response in breast cancer.
abstract: Atypical chemokine receptors (ACKRs) function as endpoint regulators of chemokine gradients. These non-signaling receptors that are transiently expressed under inflammatory conditions have critical roles in the control or maintenance of immune responses. Alternatively, here, CCRL2 (ACKR5) expression was determined to be constitutive in breast cancer cells. Increased amount of CCRL2 was also found in breast tumor tissues with high immune infiltration. Its expression was upregulated in the presence of pro-inflammatory cytokines, IL-1β, TNF-α, IL-6, and especially IFN-γ⋅ Moreover, an alternative transcript of CCRL2 gene, CRAM-A, was specifically expressed in a transient fashion under the influence of IFN-γ. CRAM-A expression was also positively correlated with the presence of IFN-γ mRNA in patient samples. CCRL2-associated chemotactic molecules, chemerin, CCL19 and CCL5, were also detected in cancer tissues and CCL5 mRNA level was correlated with that of CRAM-A and IFN-γ. Hence, in breast cancer, CRAM-A becomes specifically upregulated under inflammatory stimuli and may serve as a potential marker of immune response.
authors.affiliation: Department of Basic Oncology, Hacettepe University Cancer Institute, Ankara, Turkey.
authors.forename: Parisa
authors.initials: P
authors.lastname: Sarmadi
authors.affiliation: Department of Basic Oncology, Hacettepe University Cancer Institute, Ankara, Turkey.
authors.forename: Gurcan
authors.initials: G
authors.lastname: Tunali
authors.affiliation: Department of Pathology, Medical Faculty, Gazi University, Ankara, Turkey.
authors.forename: Guldal
authors.initials: G
authors.lastname: Esendagli-Yilmaz
authors.affiliation: Department of General Surgery, Diskapi Yildirim Beyazit Training and Research Hospital, Ankara, Turkey.
authors.forename: Kerim Bora
authors.initials: KB
authors.lastname: Yilmaz
authors.affiliation: Department of Basic Oncology, Hacettepe University Cancer Institute, Ankara, Turkey. Electronic address: gunes.esendagli@lycos.com.
authors.forename: Gunes
authors.initials: G
authors.lastname: Esendagli
mesh_terms: D014408:Biomarkers, Tumor / Q000032:analysis; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000235:genetics / Q000276:immunology / Q000473:pathology*; D018270:Carcinoma, Ductal, Breast / Q000235:genetics / Q000276:immunology / Q000473:pathology*; D045744:Cell Line, Tumor; D005260:Female; D005434:Flow Cytometry; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics / Q000276:immunology*; D006801:Humans; D007150:Immunohistochemistry; D007249:Inflammation / Q000235:genetics / Q000276:immunology; D007371:Interferon-gamma / Q000276:immunology*; D060888:Real-Time Polymerase Chain Reaction; D054388:Receptors, CCR / Q000235:genetics* / Q000276:immunology; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D014408:Biomarkers, Tumor; C487531:CCRL2 protein, human; D054388:Receptors, CCR; D007371:Interferon-gamma
keywords: Atypical chemokine receptor; Breast cancer; CCRL2; Decoy receptor; Immune response; Inflammation