PMID- 28433655
OWN - NLM
STAT- MEDLINE
DCOM- 20180309
LR  - 20220321
IS  - 1876-7753 (Electronic)
IS  - 1873-5061 (Print)
IS  - 1873-5061 (Linking)
VI  - 21
DP  - 2017 May
TI  - Targeting sarcoma tumor-initiating cells through differentiation therapy.
PG  - 117-123
LID - S1873-5061(17)30070-3 [pii]
LID - 10.1016/j.scr.2017.04.004 [doi]
AB  - Human leukocyte antigen class I (HLA-I) down-regulation has been reported in many 
      human cancers to be associated with poor clinical outcome. However, its 
      connection to tumor-initiating cells (TICs) remains unknown. In this study, we 
      report that HLA-I is down-regulated in a subpopulation of cells that have high 
      tumor initiating capacity in different types of human sarcomas. Detailed 
      characterization revealed their distinct molecular profiles regarding 
      proliferation, apoptosis and stemness programs. Notably, these TICs can be 
      induced to differentiate along distinct mesenchymal lineages, including the 
      osteogenic pathway. The retinoic acid receptor signaling pathway is overexpressed 
      in HLA-1 negative TICs. All-trans retinoic acid treatment successfully induced 
      osteogenic differentiation of this subpopulation, in vitro and in vivo, resulting 
      in significantly decreased tumor formation. Thus, our findings indicate 
      down-regulated HLA-I is a shared feature of TICs in a variety of human sarcomas, 
      and differentiation therapy strategies may specifically target undifferentiated 
      TICs and inhibit tumor formation.
CI  - Copyright (c) 2017 The Authors. Published by Elsevier B.V. All rights reserved.
FAU - Han, Dan
AU  - Han D
AD  - Department of Pathology, Icahn School of Medicine at Mount Sinai, New York, NY 
      10029, USA.
FAU - Rodriguez-Bravo, Veronica
AU  - Rodriguez-Bravo V
AD  - Department of Pathology, Icahn School of Medicine at Mount Sinai, New York, NY 
      10029, USA.
FAU - Charytonowicz, Elizabeth
AU  - Charytonowicz E
AD  - Department of Pathology, Icahn School of Medicine at Mount Sinai, New York, NY 
      10029, USA.
FAU - Demicco, Elizabeth
AU  - Demicco E
AD  - Department of Pathology, Icahn School of Medicine at Mount Sinai, New York, NY 
      10029, USA.
FAU - Domingo-Domenech, Josep
AU  - Domingo-Domenech J
AD  - Department of Pathology, Icahn School of Medicine at Mount Sinai, New York, NY 
      10029, USA.
FAU - Maki, Robert G
AU  - Maki RG
AD  - Department of Hematology-Oncology, Icahn School of Medicine at Mount Sinai, New 
      York, NY 10029, USA.
FAU - Cordon-Cardo, Carlos
AU  - Cordon-Cardo C
AD  - Department of Pathology, Icahn School of Medicine at Mount Sinai, New York, NY 
      10029, USA. Electronic address: carlos.cordon-cardo@mssm.edu.
LA  - eng
GR  - K22 CA207458/CA/NCI NIH HHS/United States
GR  - P01 CA087497/CA/NCI NIH HHS/United States
GR  - R01 CA207311/CA/NCI NIH HHS/United States
GR  - U54 OD020353/OD/NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20170413
PL  - England
TA  - Stem Cell Res
JT  - Stem cell research
JID - 101316957
RN  - 0 (HLA Antigens)
RN  - 5688UTC01R (Tretinoin)
SB  - IM
MH  - Carcinogenesis/drug effects/genetics/pathology
MH  - *Cell Differentiation/drug effects
MH  - Cell Line, Tumor
MH  - Gene Expression Profiling
MH  - Gene Expression Regulation, Neoplastic/drug effects
MH  - HLA Antigens/immunology
MH  - Humans
MH  - Neoplastic Stem Cells/drug effects/*pathology
MH  - Osteogenesis/drug effects/genetics
MH  - Phenotype
MH  - Sarcoma/genetics/*pathology/*therapy
MH  - Tretinoin/pharmacology
PMC - PMC5988213
MID - NIHMS870269
OTO - NOTNLM
OT  - Human leukocyte antigen class I
OT  - Sarcomas
OT  - Tumor-initiating cells
COIS- Conflict of interest The authors declare no competing financial interests.
EDAT- 2017/04/24 06:00
MHDA- 2018/03/10 06:00
PMCR- 2018/06/05
CRDT- 2017/04/24 06:00
PHST- 2016/10/17 00:00 [received]
PHST- 2017/02/23 00:00 [revised]
PHST- 2017/04/11 00:00 [accepted]
PHST- 2017/04/24 06:00 [pubmed]
PHST- 2018/03/10 06:00 [medline]
PHST- 2017/04/24 06:00 [entrez]
PHST- 2018/06/05 00:00 [pmc-release]
AID - S1873-5061(17)30070-3 [pii]
AID - 10.1016/j.scr.2017.04.004 [doi]
PST - ppublish
SO  - Stem Cell Res. 2017 May;21:117-123. doi: 10.1016/j.scr.2017.04.004. Epub 2017 Apr 
      13.