title: Atypical chemokine receptors in cancer: friends or foes?
abstract: The chemokine system is a fundamental component of cancer-related inflammation involved in all stages of cancer development. It controls not only leukocyte infiltration in primary tumors but also angiogenesis, cancer cell proliferation, and migration to metastatic sites. Atypical chemokine receptors are a new, emerging class of regulators of the chemokine system. They control chemokine bioavailability by scavenging, transporting, or storing chemokines. They can also regulate the activity of canonical chemokine receptors with which they share the ligands by forming heterodimers or by modulating their expression levels or signaling activity. Here, we summarize recent results about the role of these receptors (atypical chemokine receptor 1/Duffy antigen receptor for chemokine, atypical chemokine receptor 2/D6, atypical chemokine receptor 3/CXC-chemokine receptor 7, and atypical chemokine receptor 4/CC-chemokine receptor-like 1) on the tumorigenesis process, indicating that their effects are strictly dependent on the cell type on which they are expressed and on their coexpression with other chemokine receptors. Indeed, atypical chemokine receptors inhibit tumor growth and progression through their activity as negative regulators of chemokine bioavailability, whereas, on the contrary, they can promote tumorigenesis when they regulate the signaling of other chemokine receptors, such as CXC-chemokine receptor 4. Thus, atypical chemokine receptors are key components of the regulatory network of inflammation and immunity in cancer and may have a major effect on anti-inflammatory and immunotherapeutic strategies.
authors.affiliation: Humanitas Clinical and Research Center, Rozzano, Italy; Department of Medical Biotechnologies and Translational Medicine, Università degli Studi di Milano, Rozzano, Italy; and.
authors.forename: Matteo
authors.initials: M
authors.lastname: Massara
authors.affiliation: Humanitas Clinical and Research Center, Rozzano, Italy; Department of Medical Biotechnologies and Translational Medicine, Università degli Studi di Milano, Rozzano, Italy; and.
authors.forename: Ornella
authors.initials: O
authors.lastname: Bonavita
authors.affiliation: Humanitas Clinical and Research Center, Rozzano, Italy; Department of Biomedical Sciences, Humanitas University, Rozzano, Italy.
authors.forename: Alberto
authors.initials: A
authors.lastname: Mantovani
authors.affiliation: Humanitas Clinical and Research Center, Rozzano, Italy; Department of Medical Biotechnologies and Translational Medicine, Università degli Studi di Milano, Rozzano, Italy; and.
authors.forename: Massimo
authors.initials: M
authors.lastname: Locati
authors.affiliation: Humanitas Clinical and Research Center, Rozzano, Italy; Department of Biomedical Sciences, Humanitas University, Rozzano, Italy raffaella.bonecchi@humanitasresearch.it.
authors.forename: Raffaella
authors.initials: R
authors.lastname: Bonecchi
mesh_terms: D000818:Animals; D063646:Carcinogenesis / Q000378:metabolism / Q000473:pathology; D018925:Chemokines / Q000378:metabolism; D006801:Humans; D008954:Models, Biological; D009369:Neoplasms / Q000378:metabolism*; D019707:Receptors, Chemokine / Q000378:metabolism*
chemical_list: D018925:Chemokines; D019707:Receptors, Chemokine
keywords: cancer-related inflammation; leukocytes; metastasis; tumor immunology