Blockade of CD47-Mediated Cathepsin S/Protease-Activated Receptor 2 Signaling Provides a Therapeutic Target for Hepatocellular Carcinoma

被引：230

作者：

Lee, Terence Kin-Wah ^{[1
,2
]}

Cheung, Vincent Chi-Ho ^{[1
,2
]}

Lu, Ping ^{[1
,2
]}

Lau, Eunice Yuen Ting ^{[1
,2
]}

Ma, Stephanie ^{[1
,3
]}

Tang, Kwan Ho ^{[2
]}

Tong, Man ^{[3
]}

Lo, Jessica ^{[1
,2
]}

Ng, Irene Oi Lin ^{[1
,2
]}

机构：

[1] Univ Hong Kong, State Key Lab Liver Res, Pokfulam, Hong Kong, Peoples R China

[2] Univ Hong Kong, Li Ka Shing Fac Med, Dept Pathol, Pokfulam, Hong Kong, Peoples R China

[3] Univ Hong Kong, Li Ka Shing Fac Med, Dept Anat, Pokfulam, Hong Kong, Peoples R China

来源：

HEPATOLOGY | 2014年 / 60卷 / 01期

基金：

中国国家自然科学基金;

关键词：

TUMOR-INITIATING CELLS; CANCER STEM-CELLS; REGULATORY PROTEIN-ALPHA; ACUTE MYELOID-LEUKEMIA; HUMAN LIVER-CANCER; SELF-RENEWAL; CD47; IDENTIFICATION; ADHESION; FEATURES;

D O I：

10.1002/hep.27070

中图分类号：

R57 [消化系及腹部疾病];

学科分类号：

100201 [内科学];

摘要：

Identification of therapeutic targets against tumor-initiating cells (TICs) is a priority in the development of new therapeutic paradigms against cancer. We enriched a TIC population capable of tumor initiation and self-renewal by serial passages of hepatospheres with chemotherapeutic agents. In chemoresistant hepatospheres, CD47 was found to be up-regulated, when compared with differentiated progenies. CD47 is preferentially expressed in liver TICs, which contributed to tumor initiation, self-renewal, and metastasis and significantly affected patients' clinical outcome. Knockdown of CD47 suppressed stem/progenitor cell characteristics. CD47 1 hepatocellular carcinoma (HCC) cells preferentially secreted cathepsin S (CTSS), which regulates liver TICs through the CTSS/protease-activated receptor 2 (PAR2) loop. Suppression of CD47 by morpholino approach suppressed growth of HCC in vivo and exerted a chemosensitization effect through blockade of CTSS/PAR2 signaling. Conclusion: These data suggest that CD47 may be an attractive therapeutic target for HCC therapy.

引用

页码：179 / 191

页数：13

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