Cancer Management and Research (Nov 2020)
Adipose-Derived Stem Cells Promote Proliferation and Invasion in Cervical Cancer by Targeting the HGF/c-MET Pathway
Abstract
Yongning Zhai,1,2,* Wangfei Wu,3,* Xiaowei Xi,4 Rongbin Yu1 1Department of Epidemiology, School of Public Health, Nanjing Medical University, Nanjing 211166, People’s Republic of China; 2Department of Gynecology, Women’s Hospital of Nanjing Medical University, Nanjing Maternity and Child Health Care Hospital, Nanjing 210004, People’s Republic of China; 3Department of Pathology, Women’s Hospital of Nanjing Medical University, Nanjing Maternity and Child Health Care Hospital, Nanjing 210004, People’s Republic of China; 4Department of Obstetrics and Gynecology, Shanghai General Hospital of Nanjing Medical University, Shanghai 200080, People’s Republic of China*These authors contributed equally to this workCorrespondence: Rongbin YuDepartment of Epidemiology, School of Public Health, Nanjing Medical University, 101 Longmian Road, Nanjing 211166, People’s Republic of ChinaEmail [email protected] XiDepartment of Obstetrics and Gynecology, Shanghai General Hospital of Nanjing Medical University, Shanghai 200080, People’s Republic of ChinaEmail [email protected]: Cervical cancer is a serious female malignancy affecting women’s health worldwide. The HGF/c-MET signaling pathway is activated in cervical cancer. Adipose-derived stem cells (ADSCs) with multipotential differentiation can carry out paracrine secretion of hepatocyte growth factor (HGF). Here, we investigated the effect and underlying mechanism of ADSCs on the promotion and invasion of cervical cancer in vitro and in vivo.Materials and Methods: ADSCs were isolated, identified, and co-cultured with cervical cancer cells. HGF was detected using ELISA, and the HGF and c-MET signaling pathway was assessed with Western blot. The proliferation and invasion of human cervical cancer cell lines (HeLa and CaSki cells) were measured using CCK-8 and transwell assays. A HeLa xenograft mouse model was established to determine the effect of ADSCs on tumor growth in vivo.Results: ADSCs secreted a high level of HGF into the supernatant, while co-culture of ADSCs and cervical cancer cells increased the supernatant level of HGF. The HGF/c-MET pathway was activated in HeLa and CaSki cells co-cultured with ADSCs. Both co-culture with ADSCs and use of ADSC-derived conditioned medium (ADSCs-CM) significantly promoted the proliferation and invasion of cervical cancer cells in vitro, an effect that was reduced by inhibiting tumor cell c-MET expression. Furthermore, ADSCs-CM promoted HeLa cervical tumor growth in vivo, which could be suppressed by intratumoral c-MET siRNA injection.Conclusion: ADSCs promote cervical cancer growth and invasion through paracrine secretion of HGF and involvement of the HGF/c-MET signaling pathway.Keywords: ADSCs, cervical cancer, paracrine, proliferation, HGF, c-MET
