Open AccessTherapeutic targeting of the thrombospondin‐1 receptor CD47 to treat liver cancer
Author(s) -
Roberts David D.,
Kaur Sukhbir,
SotoPantoja David R.
Publication year - 2015
Publication title -
journal of cell communication and signaling
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.329
H-Index - 44
eISSN - 1873-961X
pISSN - 1873-9601
DOI - 10.1007/s12079-015-0283-9
Subject(s) - cd47 , thrombospondin 1 , cancer research , matricellular protein , medicine , blockade , signal transduction , cancer , immune checkpoint , immunology , receptor , antibody , biology , angiogenesis , microbiology and biotechnology , extracellular matrix
CD47 is a signaling receptor for the matricellular protein thrombospondin‐1 and a counter‐receptor for signal regulatory protein‐α (SIRPα) on macrophages. Following its initial discovery in 1992 as a cell surface protein that is over‐expressed by ovarian carcinoma, elevated CD47 expression has emerged as a negative prognostic factor for a variety of cancers. CD47 is also a potential therapeutic target based on the ability of CD47 blockade to cause regression of tumors in mice, and a humanized CD47 antibody has recently entered phase I clinical trials. CD47 blockade may control tumor growth by inhibiting thrombospondin‐1 signaling or by preventing inhibitory SIRPα signaling in tumor‐associated macrophages. A recent publication by Lee et al. (Hepatology 60:179–191, 2014) provides evidence that blocking CD47 signaling specifically depletes tumor‐initiating stem cells in hepatocellular carcinoma and implicates cathepsin‐S/protease‐activated receptor‐2 signaling in mediating this therapeutic response.