Open AccessFractalkine/CX3CL1 induced intercellular adhesion molecule-1-dependent tumor metastasis through the CX3CR1/PI3K/Akt/NF-κB pathway in human osteosarcoma
Author(s) -
Ju-Fang Liu,
Ya Ting Tsao,
ChunHan Hou
Publication year - 2016
Publication title -
oncotarget
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.373
H-Index - 127
ISSN - 1949-2553
DOI - 10.18632/oncotarget.11250
Subject(s) - osteosarcoma , cx3cl1 , medicine , cancer research , metastasis , cx3cr1 , cell adhesion molecule , protein kinase b , cell adhesion , icam 1 , cell migration , cell , pi3k/akt/mtor pathway , immunology , pathology , chemokine , cancer , signal transduction , biology , microbiology and biotechnology , inflammation , chemokine receptor , genetics
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.