Oncotarget

Research Papers:

Fractalkine/CX3CL1 induced intercellular adhesion molecule1dependent tumor metastasis through the CX3CR1/PI3K/Akt/NFκB pathway in human osteosarcoma

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Oncotarget. 2017; 8:54136-54148. https://doi.org/10.18632/oncotarget.11250

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Ju-Fang Liu1, Ya-Ting Tsao2 and Chun-Han Hou2

1Central Laboratory, Shin-Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan

2Department of Orthopedic Surgery, National Taiwan University Hospital, Taipei, Taiwan

Correspondence to:

Chun-Han Hou, email: [email protected]

Keywords: fractalkine, osteosarcoma, metastasis, cell migration, ICAM-1

Received: February 23, 2016    Accepted: July 09, 2016    Published: August 12, 2016

ABSTRACT

Osteosarcoma is the most common primary bone tumor in children and teens. The exact molecular mechanism underlying osteosarcoma progression still remains unclear. The CX3CL1/fractalkine has been implicated in various tumors but not in osteosarcoma. This study is the first to show that fractalkine promotes osteosarcoma metastasis by promoting cell migration. Fractalkine expression was higher in osteosarcoma cell lines than in normal osteoblasts. Fractalkine induced cell migration by upregulating intercellular adhesion molecule-1 (ICAM-1) expression via CX3CR1/PI3K/Akt/NF-κB pathway in human osteosarcoma cells. Knockdown of fractalkine expression markedly inhibited cell migration and lung metastasis in osteosarcoma. Finally, we showed a clinical correlation between CX3CL1 expression and ICAM-1 expression as well as tumor stage in human osteosarcoma tissues. In conclusion, our results indicate that fractalkine promotes cell migration and metastasis of osteosarcoma by upregulating ICAM-1 expression. Thus, fractalkine could serve a novel therapeutic target for preventing osteosarcoma metastasis.