Role of chemokine CX3CL1 in progression of multiple myeloma via CX3CR1 in bone microenvironments

Wada,Akinori; Ito,Aya; Iitsuka,Hirofumi; Tsuneyama,Koichi; Miyazono,Takayoshi; Murakami,Jun; Shibahara,Naotoshi; Sakurai,Hiroaki; Saiki,Ikuo; Nakayama,Takashi; Yoshie,Osamu; Koizumi,Keiichi; Sugiyama,Toshiro

doi:10.3892/or.2015.3941

Role of chemokine CX3CL1 in progression of multiple myeloma via CX3CR1 in bone microenvironments

Authors:
- Akinori Wada
- Aya Ito
- Hirofumi Iitsuka
- Koichi Tsuneyama
- Takayoshi Miyazono
- Jun Murakami
- Naotoshi Shibahara
- Hiroaki Sakurai
- Ikuo Saiki
- Takashi Nakayama
- Osamu Yoshie
- Keiichi Koizumi
- Toshiro Sugiyama
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Affiliations: Department of Gastroenterology and Hematology, Graduate School of Medicine and Pharmaceutical Science, University of Toyama, Toyama, Japan, Division of Kampo Diagnostics, Institute of Natural Medicine, University of Toyama, Toyama, Japan, Department of Cancer Cell Biology, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama, Japan, Division of Pathogenic Biochemistry, Institute of Natural Medicine, University of Toyama, Toyama, Japan, Division of Chemotherapy, Kinki University School of Pharmaceutical Sciences, Osaka, Japan, Department of Microbiology, Kinki University Faculty of Medicine, Osaka, Japan
Published online on: April 28, 2015 https://doi.org/10.3892/or.2015.3941
Pages: 2935-2939

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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.

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