2. Academic Validation
  3. Retinoids Decrease Soluble MICA Concentration by Inhibiting the Enzymatic Activity of ADAM9 and ADAM10

Retinoids Decrease Soluble MICA Concentration by Inhibiting the Enzymatic Activity of ADAM9 and ADAM10

  • Anticancer Res. 2021 May;41(5):2307-2320. doi: 10.21873/anticanres.15006.
Yumi Otoyama 1,  Jun Arai 2,  Kaku Goto 3,  Hisako Nozawa 1,  Ryo Nakagawa 4,  Ryosuke Muroyama 4,  Ikuya Sugiura 1,  Yoko Nakajima 1,  Atsushi Kajiwara 1,  Masayuki Tojo 1,  Yuki Ichikawa 1,  Shojiro Uozumi 1,  Yuu Shimozuma 1,  Manabu Uchikoshi 1,  Masashi Sakaki 1,  Naoya Kato 4,  Hitoshi Yoshida 1
Affiliations

Affiliations

  • 1 Division of Gastroenterology, Department of Medicine, Showa University School of Medicine, Tokyo, Japan.
  • 2 Division of Gastroenterology, Department of Medicine, Showa University School of Medicine, Tokyo, Japan; [email protected].
  • 3 Institut de Recherche sur les Maladies Virales et Hépatiques, INSERM, Strasbourg, France.
  • 4 Department of Gastroenterology, Graduate School of Medicine, Chiba University, Chiba, Japan.
PMID: 33952456 DOI: 10.21873/anticanres.15006
Abstract

Background/aim: The association between MHC class I polypeptide-related sequence A (MICA) and hepatocellular carcinoma (HCC) development was identified in our previous genome-wide association study. Decreasing soluble MICA (sMICA) through MICA sheddases suppression facilitates natural killer (NK) cell-mediated cytotoxicity. The expression of ADAM9 in HCC has been correlated with poor prognosis, and our recent study showed that its suppression contributes to Cancer elimination by decreasing sMICA.

Materials and methods: Human HCC cell line PLC/PRF/5 and HepG2 cells were used. sMICA levels were measured by ELISA. Expression of retinoid X receptors (RXRs) and retinoic acid receptors (RARs) was knocked down by siRNA.

Results: In our screening of FDA-approved drugs in vitro, retinoids were found to be efficient ADAM9 and ADAM10 inhibitors. Treatment with retinoids reduced sMICA levels in human HCC cells. Interestingly, the effects were abrogated by depletion of the retinoid receptor RXRα.

Conclusion: Retinoids can be potential novel agents for HCC treatment.

Keywords

ADAM10; ADAM9; HCC treatment; MICA; retinoids.

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