Zhai Yongning, Wu Wangfei, Xi Xiaowei, Yu Rongbin
Department of Epidemiology, School of Public Health, Nanjing Medical University, Nanjing 211166, People's Republic of China.
Department of Gynecology, Women's Hospital of Nanjing Medical University, Nanjing Maternity and Child Health Care Hospital, Nanjing 210004, People's Republic of China.
Cancer Manag Res. 2020 Nov 18;12:11823-11832. doi: 10.2147/CMAR.S277130. eCollection 2020.
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.
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.
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.
ADSCs promote cervical cancer growth and invasion through paracrine secretion of HGF and involvement of the HGF/c-MET signaling pathway.
宫颈癌是一种严重的女性恶性肿瘤，影响着全球女性的健康。HGF/c-MET信号通路在宫颈癌中被激活。具有多能分化能力的脂肪来源干细胞（ADSCs）可旁分泌肝细胞生长因子（HGF）。在此，我们研究了ADSCs在体外和体内对宫颈癌增殖和侵袭的影响及潜在机制。
分离、鉴定ADSCs，并将其与宫颈癌细胞共培养。采用ELISA检测HGF，用蛋白质印迹法评估HGF和c-MET信号通路。使用CCK-8和Transwell实验检测人宫颈癌细胞系（HeLa和CaSki细胞）的增殖和侵袭能力。建立HeLa异种移植小鼠模型以确定ADSCs对体内肿瘤生长的影响。
ADSCs向上清液中分泌高水平的HGF，而ADSCs与宫颈癌细胞共培养可增加上清液中HGF的水平。在与ADSCs共培养的HeLa和CaSki细胞中，HGF/c-MET通路被激活。与ADSCs共培养以及使用ADSC条件培养基（ADSCs-CM）均显著促进体外宫颈癌细胞的增殖和侵袭，抑制肿瘤细胞c-MET表达可减弱该作用。此外，ADSCs-CM促进体内HeLa宫颈肿瘤生长，瘤内注射c-MET siRNA可抑制其生长。
ADSCs通过旁分泌HGF及参与HGF/c-MET信号通路促进宫颈癌的生长和侵袭。
