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APMIS. 2015 Oct;123(10):837-46. doi: 10.1111/apm.12427. Epub 2015 Aug 14.

Leukemia inhibitory factor promotes tumor growth and metastasis in human osteosarcoma via activating STAT3.

Author information

  • 1Department of Orthopedics, Liaocheng Second People's Hospital, Linqing City, Shandong Province, China.
  • 2Department of Orthopedics, The People's Hospital of Zhangqiu City, Zhangqiu City, Shandong Province, China.
  • 3Department of Pathology, The People's Hospital of Zhangqiu City, Zhangqiu City, Shandong Province, China.
  • 4Department of Pediatric Gastrointestinal Surgery, The People's Hospital of Zhangqiu City, Zhangqiu City, Shandong Province, China.
  • 5Department of Interventional Radiology, Affiliated Hospital of Jiangnan University and Wuxi 4th People's Hospital, Wuxi City, Jiangsu Province, China.


The leukemia inhibitory factor (LIF) has been demonstrated to be an oncogene and participated in multiple procedures during the initiation and progression of many human malignancies. However, the role of LIF in osteosarcoma is still largely unknown. Here, we performed a series of in vitro and in vivo experiments to investigate the expression and biological functions of LIF in osteosarcoma. Compared to that in the non-cancerous tissues, LIF was significantly overexpressed in a panel of 68 osteosarcoma samples (p < 0.0001). Moreover, the overexpression of LIF was significantly correlated with advanced tumor stage, larger tumor size, and shorter overall survival. In addition, knockdown of LIF notably suppressed the proliferation and invasion of osteosarcoma via blocking the STAT3 signal pathway; in contrast, treatment with the recombinant LIF protein significantly promoted the growth and invasion of osteosarcoma through enhancing the phosphorylation of STAT3, which can be partially neutralized by the STAT3 inhibitor, HO-3867. In conclusion, we demonstrated that LIF was frequently overexpressed in osteosarcoma, which could promote the growth and invasion through activating the STAT3 pathway. Our findings proposed that LIF might be a potent therapeutic target for osteosarcoma.


Osteosarcoma; STAT3; invasion; leukemia inhibitory factor; proliferation

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