Adipose-derived mesenchymal stem cells promote osteosarcoma proliferation and metastasis by activating the STAT3 pathway

// Yan Wang 1, * , Yijing Chu 2, * , Bin Yue 1 , Xuexiao Ma 1 , Guoqing Zhang 1 , Hongfei Xiang 1 , Yong Liu 1 , Tianrui Wang 1 , Xiaolin Wu 1 , Bohua Chen 1 1 Department of Orthopaedic Surgery, the Affiliated Hospital of Qingdao University, Qingdao, China 2 Department of Obstetrics and Gynecology, the Affiliated Hospital of Qingdao University, Qingdao, China * These authors have contributed equally to this work Correspondence to: Bohua Chen, email: bhchen@hotmail.com Keywords: osteosarcoma, adipose-derived mesenchymal stem cells, tumour microenvironment, signal transducer and activator of transcription 3, matrix metalloproteinase Received: July 25, 2016      Accepted: February 06, 2017      Published: March 03, 2017 ABSTRACT Osteosarcoma is the most common primary bone malignancy in children and young adults, but the role of adipose-derived mesenchymal stem cells (ADSCs) in the rapid progression of osteosarcoma is still unclear. Here, we found that ADSCs promoted tumour growth and invasion by increasing matrix metalloproteinase 2/9 (MMP2/9) expression in tumour cells. The persistent activation of signal transducer and activator of transcription 3 (STAT3) has been shown to directly promote tumour growth by mediating a wide spectrum of cellular responses, and STAT3 activation was detected in osteosarcoma cells co-cultured with ADSCs or treated with ADSC-conditioned medium. Furthermore, siRNA-mediated STAT3 inhibition in osteosarcoma cells decreased cell proliferation and invasion and down-regulated MMP2/9 expression. In addition, a nude mouse model of osteosarcoma was established by injecting luciferase-labelled MG63 cells into the tibia. As shown in in vivo bioluminescence images, ADSCs promoted tumour cell proliferation, invasion progression and metastasis. STAT3 inhibition attenuated tumour growth and metastasis and prolonged the survival of these mice. After the siRNA treatment, the MMP2, MMP9 and Ki67 levels decreased. Based on these data, stromal ADSCs promote osteosarcoma progression by increasing STAT3 signalling-mediated MMP2/9 expression.