Amphiregulin enhances intercellular adhesion molecule-1 expression and promotes tumor metastasis in human osteosarcoma
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Ju-Fang Liu1, Ya-Ting Tsao2, Chun-Han Hou2
1Central Laboratory, Shin-Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan
2Department of Orthopedic Surgery, National Taiwan University Hospital, Taipei, Taiwan
Chun-Han Hou, e-mail: [email protected]
Keywords: amphiregulin, osteosarcoma metastasis, cell migration, ICAM-1, EGFR
Received: May 21, 2015 Accepted: September 13, 2015 Published: October 19, 2015
Osteosarcoma is a common, high malignant, and metastatic bone cancer. Amphiregulin (AREG) has been associated with cancer cellular activities. However, the effect of AREG on metastasis activity in human osteosarcoma cells has yet to be determined. We determined that AREG increases the expression of intercellular adhesion molecule-1 (ICAM-1) through PI3K/Akt signaling pathway via its interaction with the epidermal growth factor receptor, thus resulting in the enhanced cell migration of osteosarcoma. Furthermore, AREG stimulation increased the association of NF-κB to ICAM-1 promoter which then up-regulated ICAM-1 expression. Finally, we observed that shRNA silencing of AREG decreased osteosarcoma metastasis in vivo. Our findings revealed a relationship between osteosarcoma metastatic potential and AREG expression and the modulating effect of AREG on ICAM-1 expression.
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