Leukotriene receptor antagonists enhance HCC treatment efficacy by inhibiting ADAMs and suppressing MICA shedding.

Cancer Immunology, Immunotherapy : CII
Jun AraiHitoshi Yoshida

Abstract

In our previous genome-wide association study, we demonstrated the association between MHC class I-related chain A (MICA) and hepatocellular carcinoma (HCC) development in patients with chronic hepatitis C. Increasing membrane-bound MICA (mMICA) in cancer cells by reducing MICA sheddases facilitates natural killer (NK) cell-mediated cytotoxicity. Our recent study clarified that A disintegrin and metalloproteases (ADAM), including ADAM9, are MICA sheddases in HCC, and that the suppression of ADAMs increases mMICA, demonstrating the rationality of mMICA-NK targeted therapy. Furthermore, we showed that regorafenib suppresses ADAM9 transcriptionally and translationally. A library of FDA-approved drugs was screened for more efficient inhibitors of ADAM9. Flow cytometry evaluation of the expression of mMICA after treatment with various candidate drugs identified leukotriene receptor antagonists as potential ADAM9 inhibitors. Furthermore, leukotriene receptor antagonists alone or in combination with regorafenib upregulated mMICA, which was in turn downregulated by leukotriene C4 and D4 via ADAM9 function. Our study demonstrates that leukotriene receptor antagonists could be developed as novel drugs for immunological control and suppre...Continue Reading

References

Oct 9, 2002·The Journal of Immunology : Official Journal of the American Association of Immunologists·Helmut R SalihAlexander Steinle
Apr 15, 2004·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Valérie Capra
Jun 19, 2004·Cancer Research·Yasushi ShintaniNariaki Matsuura
Jun 28, 2008·BMC Cancer·Florian R FritzscheGlen Kristiansen
Jan 13, 2010·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·Cecilia MagnussonAnita Sjölander
Jan 26, 2010·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Keisuke KohgaNorio Hayashi
Jul 16, 2010·Nature Reviews. Gastroenterology & Hepatology·Ju Dong Yang, Lewis R Roberts
Sep 8, 2010·Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine·Yan ZhouShenghua Jie
Sep 9, 2010·International Journal of Cancer. Journal International Du Cancer·Cecilia MagnussonAnita Sjölander
Apr 27, 2013·Molecular Cancer Therapeutics·Lotfi Abou-ElkacemWiltrud Lederle
Oct 2, 2014·Journal of Gastroenterology·Kaku Goto, Naoya Kato
Dec 10, 2015·Current Drug Targets·Gianluigi MazzoccoliManlio Vinciguerra
Oct 22, 2017·Journal of Gastroenterology and Hepatology·Jun AraiNaoya Kato
Mar 20, 2018·Cellular and Molecular Life Sciences : CMLS·Victor O OriaOliver Schilling
Jun 7, 2018·International Journal of Cancer. Journal International Du Cancer·Jun AraiNaoya Kato

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Citations

Oct 25, 2020·International Journal of Molecular Sciences·Cheng-Wei ChouYuh-Pyng Sher
Jul 6, 2021·Internal Medicine·Akihiro NakayamaHitoshi Yoshida
Aug 20, 2021·Biochemical Pharmacology·María de Luján Alvarez, Florencia Lorenzetti

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Methods Mentioned

BETA
flow cytometry
ELISA

Software Mentioned

RESORCE

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