SSX2IP promotes metastasis and chemotherapeutic resistance of hepatocellular carcinoma

Journal of Translational Medicine

Keke Huo²  Zhenggang Zhu¹  Yu Zhang³  Ying Lin²  Pu Li¹ 

[1] Shanghai Key Laboratory of Gastric Neoplasms, Department of Surgery, Shanghai Institute of Digestive Surgery, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, 197 Rui Jin Er Rd, Shanghai 200025, People’s Republic of China;State Key Laboratory of Genetic Engineering, Institute of Genetics, School of Life Sciences, Fudan University, 220 Handan Rd, Shanghai 200433, People’s Republic of China;Department of Developmental Biology, Memorial Sloan-Kettering Cancer Center, Sloan-Kettering Institute, RRL8411275 York Ave, New York, NY10065, USA

关键词: Chemotherapeutic resistance;    Metastasis;    Hepatocellular carcinoma;    SSX2IP;   

Others  :  828011
DOI  :  10.1186/1479-5876-11-52

 received in 2012-10-29, accepted in 2012-12-14,  发布年份 2013

【 摘 要 】

Background

Synovial sarcoma, X breakpoint 2 interacting protein (SSX2IP), which has been identified as an acute myeloid leukemia associated antigen, is a potential target for leukemia immunotherapy. In rodents, its homologous gene, ADIP, plays an important role in the regulation of cell adhesion and migration, underlying its potential role in promoting metastasis of other cancers.

Methods

To investigate the correlation between the expression level of SSX2IP and the clinicopathologic factors of hepatocellular carcinoma (HCC), 53 cases were studied by qPCR and statisted. To directly testing SSX2IP’s contribution to HCC in animal models, 45 nude mice were enrolled in peritoneal spreading and liver metastasis models. For the migration and invasion assays, cell culture experiments were performed using QCM^TM 24-Well Colorimetric Migration Assay Kit and Cell Invasion Assay Kit (Millipore). Moreover we examined the influence of SSX2IP overexpression on the chemosensitivity of hepatocellular carcinoma cells to two most common chemotherapy drugs (5-Fu and CDDP) using Cell counting kit-8 (CCK-8). The chemotherapeutic drugs sensitivity was evaluated by IC50 parameter.

Results

Statistical analysis of clinical cases revealed that the SSX2IP high expression group had inclinations towards larger tumor size, more tumor thrombus and shorter survival period, implying a strong correlation between the expression level of SSX2IP and HCC tumorigenesis. Consistently in abdominal cavity metastasis and liver metastasis models of immune-deficient mice, SSX2IP was able to promote the metastasis of hepatoma cells. At the cytological level, SSX2IP stimulates the wound healing, metastasis and invasion of hepatoma cells, and reduces the sensitivity of hepatoma cells to 5-Fu and CDDP.

Conclusions

Our results showed that SSX2IP promotes the development and metastasis of hepatocellular carcinoma and contributes to the drug resistance of hepatoma cells, suggesting that SSX2IP is expected to become a new diagnostic and prognostic marker and a new target of the treatment of hepatocellular carcinoma.

【 授权许可】

   
2013 Li et al; licensee BioMed Central Ltd.

【 图 表 】

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