title: Role of chemokine CX3CL1 in progression of multiple myeloma via CX3CR1 in bone microenvironments.
abstract: Several chemokines/chemokine receptors such as CXCL12, CCL3, CXCR4 and CCR1 attract multiple myelomas to specific microenvironments. In the present study, we investigated whether the CX3CL1/CX3CR1 axis is involved in the interaction of the multiple myeloma cells with their microenvironment. The expression of CX3CR1 (also known as fractalkine) was detected in three of the seven human myeloma cell lines. CX3CL1-induced phosphorylation of Akt and ERK1/2 was detected in the CX3CR1-positive cell lines, but not in the CX3CR1-negative cell lines. In addition, CX3CL1-induced cell adhesion to fibronectin and vascular cell adhesion molecule-1 (VCAM-1) in the human myeloma RPMI-8226 cell line. We also investigated whether a relationship existed between myeloma cells and osteoclasts that may function via the CX3CL1/CX3CR1 axis. Conditioned medium from CX3CL1-stimulated RPMI-8226 cells drastically increased the osteoclast differentiation. Collectively, the results from the present study support the concept of the CX3CL1-mediated activation of the progression of the multiple myeloma via CX3CR1. Thus, CX3CR1 may represent a potential therapeutic target for the treatment of multiple myeloma in a bone microenvironment.
authors.affiliation: Department of Gastroenterology and Hematology, Graduate School of Medicine and Pharmaceutical Science, University of Toyama, Toyama, Japan.
authors.forename: Akinori
authors.initials: A
authors.lastname: Wada
authors.affiliation: Division of Kampo Diagnostics, Institute of Natural Medicine, University of Toyama, Toyama, Japan.
authors.forename: Aya
authors.initials: A
authors.lastname: Ito
authors.affiliation: Division of Kampo Diagnostics, Institute of Natural Medicine, University of Toyama, Toyama, Japan.
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Iitsuka
authors.affiliation: Department of Cancer Cell Biology, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama, Japan.
authors.forename: Koichi
authors.initials: K
authors.lastname: Tsuneyama
authors.affiliation: Department of Gastroenterology and Hematology, Graduate School of Medicine and Pharmaceutical Science, University of Toyama, Toyama, Japan.
authors.forename: Takayoshi
authors.initials: T
authors.lastname: Miyazono
authors.affiliation: Department of Gastroenterology and Hematology, Graduate School of Medicine and Pharmaceutical Science, University of Toyama, Toyama, Japan.
authors.forename: Jun
authors.initials: J
authors.lastname: Murakami
authors.affiliation: Division of Kampo Diagnostics, Institute of Natural Medicine, University of Toyama, Toyama, Japan.
authors.forename: Naotoshi
authors.initials: N
authors.lastname: Shibahara
authors.affiliation: Department of Cancer Cell Biology, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama, Japan.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Sakurai
authors.affiliation: Division of Pathogenic Biochemistry, Institute of Natural Medicine, University of Toyama, Toyama, Japan.
authors.forename: Ikuo
authors.initials: I
authors.lastname: Saiki
authors.affiliation: Division of Chemotherapy, Kinki University School of Pharmaceutical Sciences, Osaka, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Nakayama
authors.affiliation: Department of Microbiology, Kinki University Faculty of Medicine, Osaka, Japan.
authors.forename: Osamu
authors.initials: O
authors.lastname: Yoshie
authors.affiliation: Division of Kampo Diagnostics, Institute of Natural Medicine, University of Toyama, Toyama, Japan.
authors.forename: Keiichi
authors.initials: K
authors.lastname: Koizumi
authors.affiliation: Department of Gastroenterology and Hematology, Graduate School of Medicine and Pharmaceutical Science, University of Toyama, Toyama, Japan.
authors.forename: Toshiro
authors.initials: T
authors.lastname: Sugiyama
mesh_terms: D001859:Bone Neoplasms / Q000235:genetics* / Q000473:pathology / Q000556:secondary; D000073883:CX3C Chemokine Receptor 1; D002448:Cell Adhesion / Q000235:genetics; D002454:Cell Differentiation / Q000235:genetics; D045744:Cell Line, Tumor; D054428:Chemokine CX3CL1 / Q000096:biosynthesis* / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D009101:Multiple Myeloma / Q000235:genetics* / Q000473:pathology; D010010:Osteoclasts / Q000378:metabolism / Q000473:pathology; D010766:Phosphorylation; D019707:Receptors, Chemokine / Q000096:biosynthesis* / Q000235:genetics; D015398:Signal Transduction; D059016:Tumor Microenvironment / Q000235:genetics; D019010:Vascular Cell Adhesion Molecule-1 / Q000235:genetics
chemical_list: D000073883:CX3C Chemokine Receptor 1; C515538:CX3CL1 protein, human; C095235:CX3CR1 protein, human; D054428:Chemokine CX3CL1; D019707:Receptors, Chemokine; D019010:Vascular Cell Adhesion Molecule-1