Journal
CANCER SCIENCE
Volume 111, Issue 8, Pages 2689-2695Publisher
WILEY
DOI: 10.1111/cas.14504
Keywords
actin; adipocyte; cancer stem cell; differentiation; osteosarcoma
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Chemoresistance is a hallmark of cancer stem cells (CSCs). To develop novel therapeutic strategies that target CSCs, we established osteosarcoma-initiating (OSi) cells by introducing the c-Myc gene into bone marrow stromal cells derived fromInk4a/ArfKO mice. These OSi cells include bipotent committed cells (similar to osteochondral progenitor cells) with a high tumorigenic activity as well as tripotent cells (similar to mesenchymal stem cells) of low tumorigenicity. We recently showed that the tripotent OSi cells are highly resistant to chemotherapeutic agents, and that depolymerization of the actin cytoskeleton in these cells induces their terminal adipocyte differentiation and suppresses their tumorigenicity. We here provide an overview of modulation of actin cytoskeleton dynamics associated with terminal adipocyte differentiation in osteosarcoma as well as discuss the prospects for new therapeutic strategies that target chemoresistant CSCs by inducing their differentiation.
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