PMID- 34790130
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20211119
IS  - 1663-9812 (Print)
IS  - 1663-9812 (Electronic)
IS  - 1663-9812 (Linking)
VI  - 12
DP  - 2021
TI  - Beta-Lapachone Attenuates BMSC-Mediated Neuroblastoma Malignant Transformation by 
      Inhibiting Gal-3/Gal-3BP/IL6 Axis.
PG  - 766909
LID - 10.3389/fphar.2021.766909 [doi]
LID - 766909
AB  - The inflammatory factor IL6 secreted by bone marrow mesenchymal stem cells 
      (BMSCs) in the tumor microenvironment (TME) facilitates the survival and 
      therapeutic resistance of neuroblastoma (NB). Here, we found that IL6 expression 
      in primary tumor tissues or bone marrow (BM) metastases was closely associated 
      with the disease risk and prognosis of NB patients. IL6 secretion from 
      immortalized BMSC (iBMSC) was directly regulated by NB cells and is involved in 
      promoting the proliferation and metastasis of NB cells. Beta-Lapachone (ARQ-501, 
      LPC), an ortho-naphthoquinone natural product, significantly prevented the 
      iBMSC-induced malignant transformation effect on NB cells through suppressing the 
      expression and secretion of IL6 from iBMSC in vitro and in vivo. Mechanistically, 
      LPC disrupted the crosstalk between NB cells and iBMSC in an NQO1-dependent 
      manner through blocking the Gal-3/Gal-3BP/IL6 axis. Our results reveal the effect 
      of iBMSC-derived IL6 on TME-induced malignant transformation of NB cells, and 
      provide theoretical basis for the clinical application of LPC as a potential IL6 
      inhibitor in high-risk refractory NB patients.
CI  - Copyright (c) 2021 Zhou, Yan, Zhou, Feng, Wang, Yang, Zhang, Yuan and Zhai.
FAU - Zhou, Yang
AU  - Zhou Y
AD  - Children's Hospital Affiliated to Zhengzhou University, Henan Children's 
      Hospital, Zhengzhou Children's Hospital, Zhengzhou University, Zhengzhou, China.
AD  - Department of Cardiothoracic Surgery, Children's Hospital Affiliated to Zhengzhou 
      University, Henan Children's Hospital, Zhengzhou Children's Hospital, Zhengzhou, 
      China.
FAU - Yan, Hui
AU  - Yan H
AD  - Children's Hospital Affiliated to Zhengzhou University, Henan Children's 
      Hospital, Zhengzhou Children's Hospital, Zhengzhou University, Zhengzhou, China.
AD  - Department of Cardiothoracic Surgery, Children's Hospital Affiliated to Zhengzhou 
      University, Henan Children's Hospital, Zhengzhou Children's Hospital, Zhengzhou, 
      China.
FAU - Zhou, Qiang
AU  - Zhou Q
AD  - Children's Hospital Affiliated to Zhengzhou University, Henan Children's 
      Hospital, Zhengzhou Children's Hospital, Zhengzhou University, Zhengzhou, China.
AD  - Department of Pathology, Children's Hospital Affiliated to Zhengzhou University, 
      Henan Children's Hospital, Zhengzhou Children's Hospital, Zhengzhou, China.
FAU - Feng, Ruiling
AU  - Feng R
AD  - Children's Hospital Affiliated to Zhengzhou University, Henan Children's 
      Hospital, Zhengzhou Children's Hospital, Zhengzhou University, Zhengzhou, China.
AD  - Department of Cardiothoracic Surgery, Children's Hospital Affiliated to Zhengzhou 
      University, Henan Children's Hospital, Zhengzhou Children's Hospital, Zhengzhou, 
      China.
FAU - Wang, Penggao
AU  - Wang P
AD  - Children's Hospital Affiliated to Zhengzhou University, Henan Children's 
      Hospital, Zhengzhou Children's Hospital, Zhengzhou University, Zhengzhou, China.
AD  - Department of Cardiothoracic Surgery, Children's Hospital Affiliated to Zhengzhou 
      University, Henan Children's Hospital, Zhengzhou Children's Hospital, Zhengzhou, 
      China.
FAU - Yang, Fang
AU  - Yang F
AD  - Children's Hospital Affiliated to Zhengzhou University, Henan Children's 
      Hospital, Zhengzhou Children's Hospital, Zhengzhou University, Zhengzhou, China.
AD  - Department of Cardiothoracic Surgery, Children's Hospital Affiliated to Zhengzhou 
      University, Henan Children's Hospital, Zhengzhou Children's Hospital, Zhengzhou, 
      China.
FAU - Zhang, Yaodong
AU  - Zhang Y
AD  - Children's Hospital Affiliated to Zhengzhou University, Henan Children's 
      Hospital, Zhengzhou Children's Hospital, Zhengzhou University, Zhengzhou, China.
FAU - Yuan, Ziqiao
AU  - Yuan Z
AD  - School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, China.
FAU - Zhai, Bo
AU  - Zhai B
AD  - Children's Hospital Affiliated to Zhengzhou University, Henan Children's 
      Hospital, Zhengzhou Children's Hospital, Zhengzhou University, Zhengzhou, China.
AD  - Department of Cardiothoracic Surgery, Children's Hospital Affiliated to Zhengzhou 
      University, Henan Children's Hospital, Zhengzhou Children's Hospital, Zhengzhou, 
      China.
LA  - eng
PT  - Journal Article
DEP - 20211101
PL  - Switzerland
TA  - Front Pharmacol
JT  - Frontiers in pharmacology
JID - 101548923
PMC - PMC8591123
OTO - NOTNLM
OT  - BMSC
OT  - IL6
OT  - beta-lapachone
OT  - neuroblastoma
OT  - tumor microenvironment
COIS- The authors declare that the research was conducted in the absence of any 
      commercial or financial relationships that could be construed as a potential 
      conflict of interest.
EDAT- 2021/11/19 06:00
MHDA- 2021/11/19 06:01
PMCR- 2021/11/01
CRDT- 2021/11/18 06:56
PHST- 2021/09/14 00:00 [received]
PHST- 2021/10/19 00:00 [accepted]
PHST- 2021/11/18 06:56 [entrez]
PHST- 2021/11/19 06:00 [pubmed]
PHST- 2021/11/19 06:01 [medline]
PHST- 2021/11/01 00:00 [pmc-release]
AID - 766909 [pii]
AID - 10.3389/fphar.2021.766909 [doi]
PST - epublish
SO  - Front Pharmacol. 2021 Nov 1;12:766909. doi: 10.3389/fphar.2021.766909. 
      eCollection 2021.