Targeting sarcoma tumor-initiating cells through differentiation therapy

Han, D., Rodriguez-Bravo, V., Charytonowicz, E., Demicco, E., Domingo-Domenech, J., Maki, R. G., Cordon-Cardo, C. (May 2017) Targeting sarcoma tumor-initiating cells through differentiation therapy. Stem Cell Res, 21. pp. 117-123. ISSN 1873-5061

DOI: 10.1016/j.scr.2017.04.004


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.

Item Type: Paper
Uncontrolled Keywords: Carcinogenesis/drug effects/genetics/pathology *Cell Differentiation/drug effects Cell Line, Tumor Gene Expression Profiling Gene Expression Regulation, Neoplastic/drug effects HLA Antigens/immunology Humans Neoplastic Stem Cells/drug effects/*pathology Osteogenesis/drug effects/genetics Phenotype Sarcoma/genetics/*pathology/*therapy Tretinoin/pharmacology *Human leukocyte antigen class I *Sarcomas *Tumor-initiating cells
Subjects: diseases & disorders > cancer > cancer types > sarcoma
CSHL Authors:
Communities: CSHL Cancer Center Program > Signal Transduction
CSHL labs > Maki lab
CSHL Cancer Center Program > Cancer Genetics and Genomics Program
Depositing User: Matt Covey
Date: May 2017
Date Deposited: 13 Jun 2018 19:16
Last Modified: 05 Nov 2020 20:59
PMCID: PMC5988213
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