PMID- 33952456
OWN - NLM
STAT- MEDLINE
DCOM- 20210517
LR  - 20210517
IS  - 1791-7530 (Electronic)
IS  - 0250-7005 (Linking)
VI  - 41
IP  - 5
DP  - 2021 May
TI  - Retinoids Decrease Soluble MICA Concentration by Inhibiting the Enzymatic 
      Activity of ADAM9 and ADAM10.
PG  - 2307-2320
LID - 10.21873/anticanres.15006 [doi]
AB  - 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 RXRalpha. CONCLUSION: Retinoids 
      can be potential novel agents for HCC treatment.
CI  - Copyright (c) 2021 International Institute of Anticancer Research (Dr. George J. 
      Delinasios), All rights reserved.
FAU - Otoyama, Yumi
AU  - Otoyama Y
AD  - Division of Gastroenterology, Department of Medicine, Showa University School of 
      Medicine, Tokyo, Japan.
FAU - Arai, Jun
AU  - Arai J
AD  - Division of Gastroenterology, Department of Medicine, Showa University School of 
      Medicine, Tokyo, Japan; araiguma10@med.showa-u.ac.jp.
FAU - Goto, Kaku
AU  - Goto K
AD  - Institut de Recherche sur les Maladies Virales et Hepatiques, INSERM, Strasbourg, 
      France.
FAU - Nozawa, Hisako
AU  - Nozawa H
AD  - Division of Gastroenterology, Department of Medicine, Showa University School of 
      Medicine, Tokyo, Japan.
FAU - Nakagawa, Ryo
AU  - Nakagawa R
AD  - Department of Gastroenterology, Graduate School of Medicine, Chiba University, 
      Chiba, Japan.
FAU - Muroyama, Ryosuke
AU  - Muroyama R
AD  - Department of Gastroenterology, Graduate School of Medicine, Chiba University, 
      Chiba, Japan.
FAU - Sugiura, Ikuya
AU  - Sugiura I
AD  - Division of Gastroenterology, Department of Medicine, Showa University School of 
      Medicine, Tokyo, Japan.
FAU - Nakajima, Yoko
AU  - Nakajima Y
AD  - Division of Gastroenterology, Department of Medicine, Showa University School of 
      Medicine, Tokyo, Japan.
FAU - Kajiwara, Atsushi
AU  - Kajiwara A
AD  - Division of Gastroenterology, Department of Medicine, Showa University School of 
      Medicine, Tokyo, Japan.
FAU - Tojo, Masayuki
AU  - Tojo M
AD  - Division of Gastroenterology, Department of Medicine, Showa University School of 
      Medicine, Tokyo, Japan.
FAU - Ichikawa, Yuki
AU  - Ichikawa Y
AD  - Division of Gastroenterology, Department of Medicine, Showa University School of 
      Medicine, Tokyo, Japan.
FAU - Uozumi, Shojiro
AU  - Uozumi S
AD  - Division of Gastroenterology, Department of Medicine, Showa University School of 
      Medicine, Tokyo, Japan.
FAU - Shimozuma, Yuu
AU  - Shimozuma Y
AD  - Division of Gastroenterology, Department of Medicine, Showa University School of 
      Medicine, Tokyo, Japan.
FAU - Uchikoshi, Manabu
AU  - Uchikoshi M
AD  - Division of Gastroenterology, Department of Medicine, Showa University School of 
      Medicine, Tokyo, Japan.
FAU - Sakaki, Masashi
AU  - Sakaki M
AD  - Division of Gastroenterology, Department of Medicine, Showa University School of 
      Medicine, Tokyo, Japan.
FAU - Kato, Naoya
AU  - Kato N
AD  - Department of Gastroenterology, Graduate School of Medicine, Chiba University, 
      Chiba, Japan.
FAU - Yoshida, Hitoshi
AU  - Yoshida H
AD  - Division of Gastroenterology, Department of Medicine, Showa University School of 
      Medicine, Tokyo, Japan.
LA  - eng
PT  - Journal Article
PL  - Greece
TA  - Anticancer Res
JT  - Anticancer research
JID - 8102988
RN  - 0 (Histocompatibility Antigens Class I)
RN  - 0 (MHC class I-related chain A)
RN  - 0 (Membrane Proteins)
RN  - 0 (Phenylurea Compounds)
RN  - 0 (Pyridines)
RN  - 0 (Retinoid X Receptors)
RN  - 0 (Retinoids)
RN  - 24T2A1DOYB (regorafenib)
RN  - EC 3.4.24.- (ADAM Proteins)
RN  - EC 3.4.24.- (ADAM9 protein, human)
RN  - EC 3.4.24.81 (ADAM10 Protein)
SB  - IM
MH  - ADAM Proteins/antagonists & inhibitors/genetics/*metabolism
MH  - ADAM10 Protein/antagonists & inhibitors/genetics/*metabolism
MH  - Biocatalysis/drug effects
MH  - Cell Line, Tumor
MH  - Cell Survival/drug effects
MH  - Drug Synergism
MH  - Hep G2 Cells
MH  - Histocompatibility Antigens Class I/genetics/*metabolism
MH  - Humans
MH  - Membrane Proteins/antagonists & inhibitors/genetics/*metabolism
MH  - Molecular Structure
MH  - Phenylurea Compounds/pharmacology
MH  - Pyridines/pharmacology
MH  - RNA Interference
MH  - Retinoid X Receptors/genetics/metabolism
MH  - Retinoids/chemistry/*pharmacology
MH  - Solubility
OTO - NOTNLM
OT  - ADAM10
OT  - ADAM9
OT  - HCC treatment
OT  - MICA
OT  - retinoids
EDAT- 2021/05/07 06:00
MHDA- 2021/05/18 06:00
CRDT- 2021/05/06 05:53
PHST- 2021/03/25 00:00 [received]
PHST- 2021/04/03 00:00 [revised]
PHST- 2021/04/05 00:00 [accepted]
PHST- 2021/05/06 05:53 [entrez]
PHST- 2021/05/07 06:00 [pubmed]
PHST- 2021/05/18 06:00 [medline]
AID - 41/5/2307 [pii]
AID - 10.21873/anticanres.15006 [doi]
PST - ppublish
SO  - Anticancer Res. 2021 May;41(5):2307-2320. doi: 10.21873/anticanres.15006.