NDLI: Blockade of CD47-mediated cathepsin S/protease-activated receptor 2 signaling provides a therapeutic target for hepatocellular carcinoma.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Lee, Terence Kin-Wah Cheung, Vincent Chi-Ho Lu, Ping Lau, Eunice Yuen Ting Ma, Stephanie Tang, Kwan Ho Tong, Man Lo, Jessica Ng, Irene Oi Lin
Description	Country affiliation: Hong Kong Author Affiliation: Lee TK ( State Key Laboratory for Liver Research, The University of Hong Kong, Pokfulam, Hong Kong)
Abstract	UNLABELLED: 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(+) 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.
File Format	HTM / HTML
ISSN	02709139
Issue Number	1
Volume Number	60
e-ISSN	15273350
Journal	Hepatology
Language	English
Publisher	Wiley
Publisher Date	2014-07-01
Publisher Place	United States
Access Restriction	Subscribed
Subject Keyword	Discipline Hepatology Antigens, Cd47 Genetics Carcinoma, Hepatocellular Therapy Cathepsins Metabolism Liver Neoplasms Receptor, Par-2 Animals Antibiotics, Antineoplastic Pharmacology Drug Therapy Cell Line, Transformed Cell Line, Tumor Doxorubicin Female Genetic Therapy Methods Humans Male Mice Mice, Inbred Balb C Mice, Nude Middle Aged Morpholinos Neoplastic Stem Cells Signal Transduction Physiology Xenograft Model Antitumor Assays Journal Article Research Support, Non-u.s. Gov't
Content Type	Text
Resource Type	Article
Subject	Hepatology

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