ADAM8 is reported to promote extracellular matrix degradation to provide conditions for tumor metastasis. However, the underlying mechanism of ADAM8 in modulating chondrosarcoma (CHS) metastasis remains unclear. We used two human CHS cell lines SW1353 and HCS-2/8 to analyze the expression profiles of ADAM8 in CHS cells compared with the normal chondrocytes. An important proteolytic enzyme MMP-13 was detected as a marker for extracellular matrix degradation in chondrocytes. Then, by silencing or overexpressing ADAM8, the effects on cell migration and invasion in SW1353 and HCS-2/8, and the downstream signal transduction pathways were evaluated. ADAM8 and MMP-13 were highly expressed, and the NF-κB pathway was activated in SW1353 and HCS-2/8 cells. Silencing ADAM8 significantly reduced the ability of cell migration and invasion, and blocked the NF-κB signaling pathway through IκBα and p65 dephosphorylation, leading to reduced NF-κB transcription activity and decreased MMP-13 expression. ADAM8 overexpression promoted these processes, which, however, were reversed by an inhibitor Bay 11–7085. Our data showed a novel regulation mechanism for ADAM8 in promoting CHS migration and invasion by activating the NF-κB/MMP-13 signaling axis. Modulation of their levels may serve as potential targets in the treatment of CHS and even other cartilage diseases.
aDepartment of Orthopaedic, Xuanwu Hospital Capital Medical University
bBeijing Northern Hospital of Weaponry Industry, Beijing
cDepartment of Orthopaedic, Inner Mongolia BaoGang Hospital, The Third Affiliated Hospital of Inner Mongolia Medical University, Baotou, People’s Republic of China
Received 15 January 2019 Revised form accepted 22 March 2019
Correspondence to Shi-Bao Lu, PhD, Department of Orthopaedic, Xuanwu Hospital Capital Medical University, No. 45, Changchun Street, Xicheng District, Beijing 100053, People’s Republic of China, Tel/fax: + 86 139 1072 7070; e-mail: email@example.com