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Therapeutic targeting of the thrombospondin-1 receptor CD47 to treat liver cancer.


ABSTRACT: CD47 is a signaling receptor for the matricellular protein thrombospondin-1 and a counter-receptor for signal regulatory protein-? (SIRP?) 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 SIRP? 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.

SUBMITTER: Roberts DD 

PROVIDER: S-EPMC4414848 | biostudies-literature | 2015 Mar

REPOSITORIES: biostudies-literature

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Therapeutic targeting of the thrombospondin-1 receptor CD47 to treat liver cancer.

Roberts David D DD   Kaur Sukhbir S   Soto-Pantoja David R DR  

Journal of cell communication and signaling 20150318 1


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 CD  ...[more]

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