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

Journal of Cell Communication and Signaling
David D RobertsDavid R Soto-Pantoja

Abstract

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.

References

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Mar 28, 2012·Proceedings of the National Academy of Sciences of the United States of America·Stephen B WillinghamIrving L Weissman
Aug 28, 2012·Proceedings of the National Academy of Sciences of the United States of America·Xi Wen ZhaoTimo K van den Berg
Aug 28, 2012·Proceedings of the National Academy of Sciences of the United States of America·David R Soto-PantojaDavid D Roberts
Dec 18, 2013·Cancer Letters·Michael L O'ConnorWei Duan
Feb 14, 2014·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Terence Kin-Wah LeeIrene Oi Lin Ng

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Citations

Mar 5, 2016·Mediators of Inflammation·Mario Orozco-MoralesOscar Arrieta
Sep 12, 2015·Journal of Cell Communication and Signaling·Bernard Perbal
Feb 23, 2020·Frontiers in Immunology·Wenting ZhangHua Jin
Mar 16, 2021·Frontiers in Oncology·Claire Deligne, Kim S Midwood

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