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The atypical chemokine receptor D6 was initially called "silent" on the basis of lack of conventional signaling events that lead to directional cell migration. It has emerged that D6 is able to bind and drive to degradative compartments most inflammatory CC chemokines and that is able to convey G-protein independent signaling events to optimize its scavenging activity. We here summarize the knowledge available today on D6 structural and signaling properties and its essential role for the control of inflammatory cells traffic and proper development of the adaptive immune response.
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http://dx.doi.org/10.1016/j.molimm.2012.08.003 | DOI Listing |
Unlabelled: Patients with myelodysplastic syndrome (MDS)/acute myeloid leukemia (AML) with high-risk features including mutations and deletions have poor outcomes due to lack of effective therapies. The atypical chemokine surface receptor C-C motif chemokine receptor-like 2 (CCRL2) is overexpressed in MDS and secondary AML (sAML) compared to healthy hematopoietic cells and we recently found that -mutated MDS/AML and AML with erythroid features express the highest levels of this receptor across MDS/AML subtypes. To illustrate the therapeutic potential of CCRL2 as a therapeutic target, we developed an anti-CCRL2 antibody-drug conjugate (ADC) by conjugating an anti-CCRL2 antibody with the cytotoxic drug pyrrolobenzodiazepine (PBD), which causes DNA double-strand breaks leading to cancer cell death.
View Article and Find Full Text PDFBiomolecules
August 2025
Research Group Genetics, Reproduction and Development, Faculty of Medicine and Pharmacy, Brussels Health Campus, Vrije Universiteit Brussel (VUB), Laarbeeklaan 103, 1090 Brussels, Belgium.
C-C motif chemokine receptor-like 2 (CCRL2) is an atypical chemokine receptor (ACKR) that binds chemerin with high affinity but lacks classical G protein-coupled signaling. Instead, it functions as a non-signaling presenter of chemerin to CMKLR1-expressing cells, modulating antitumor immunity. CCRL2 is highly expressed in the tumor microenvironment and various human cancers, and its expression has been linked to delayed tumor growth in mouse models, primarily through the chemerin/CMKLR1 axis.
View Article and Find Full Text PDFDiscov Oncol
August 2025
Department of Biochemistry, All India Institute of Medical Sciences, New Delhi, India.
This study investigates the interplay between the Atypical chemokine receptors (ACKR1)/Decoy receptor for chemokines (DARC) and key molecular markers, including CCL8, c-MYC, ALDH1, and CHEK2, in breast cancer. DARC has been implicated in various aspects of cancer progression, including tumor growth, angiogenesis, and metastasis. By analyzing the expression patterns of these markers in breast cancer tissues, we aim to understand their collective impact on tumor behaviour and identify potential therapeutic targets.
View Article and Find Full Text PDFInt J Clin Exp Pathol
July 2025
Department of Oncology, Affiliated Tumor Hospital of Nantong University Nantong 226631, Jiangsu, China.
Objectives: Gastric cancer (GC) ranks as the fourth most prevalent malignancy globally and is a leading cause of cancer-related mortality. This study aims to comprehensively investigate the pathogenesis of gastric cancer and propose innovative strategies for early diagnosis.
Methods: Leveraging data from The Cancer Genome Atlas (TCGA), we identified that hsa-miR-100-5p exhibits significantly reduced expression in gastric cancer tissues compared to normal tissues.
bioRxiv
June 2025
Research Service, Veterans Affairs Portland Health Care System, Portland OR 97239; Department of Behavioral Neuroscience, Oregon Health & Science University, Portland OR 97239 USA; Department of Psychiatry, Oregon Health & Science University, Portland OR 97239 USA.
All cells secrete extracellular vesicles (EVs) containing nucleic acid cargo, including microRNAs (miRNAs), that regulate the function of receiving cells. G protein-coupled receptors (GPCRs) affect intracellular function via multiple signaling cascades. However, the mechanisms of GPCR intercellular signaling through EV miRNA activity are unknown.
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