title: Molecular basis of differentiation therapy for soft tissue sarcomas.
abstract: Stem cells are undifferentiated precursor cells with the capacity for proliferation or terminal differentiation. Progression down the differentiation cascade results in a loss of proliferative potential in exchange for the differentiated phenotype. This balance is tightly regulated in the physiologic state. Recent studies, however, have demonstrated that during tumorigenesis, disruptions preventing terminal differentiation allow cancer cells to maintain a proliferative, precursor cell phenotype. Current therapies (i.e., chemotherapy and radiation therapy) target the actively proliferating cells in tumor masses, which in many cases inevitably induce therapy-resistant cancer cells. It is conceivable that promising therapy regimens can be developed by treating human cancers by inducing terminal differentiation, thereby restoring the interrupted pathway and shifting the balance from proliferation to differentiation. For example, osteosarcoma (OS) is a primary bone cancer caused by differentiation defects in mesenchymal stem cells (MSCs) for which several differentiation therapies have shown great promise. In this review, we discuss the various differentiation therapies in the treatment of human sarcomas with a focus on OS. Such therapies hold great promise as they not only inhibit tumorigenesis, but also avoid the adverse effects associated with conventional chemotherapy regimens. Furthermore, it is conceivable that a combination of conventional therapies with differentiation therapy should significantly improve anticancer efficacy and reduce drug-resistance in the clinical management of human cancers, including sarcomas.
authors.affiliation: Molecular Oncology Laboratory, Department of Surgery, The University of Chicago Medical Center, Chicago, IL 60637, USA.
authors.forename: Gaurav
authors.initials: G
authors.lastname: Luther
authors.affiliation: Molecular Oncology Laboratory, Department of Surgery, The University of Chicago Medical Center, Chicago, IL 60637, USA.
authors.forename: Richard
authors.initials: R
authors.lastname: Rames
authors.affiliation: Molecular Oncology Laboratory, Department of Surgery, The University of Chicago Medical Center, Chicago, IL 60637, USA.
authors.forename: Eric R
authors.initials: ER
authors.lastname: Wagner
authors.affiliation: Molecular Oncology Laboratory, Department of Surgery, The University of Chicago Medical Center, Chicago, IL 60637, USA; Stem Cell Biology and Therapy Laboratory, The Children's Hospital of Chongqing Medical University, Chongqing 400014, China.
authors.forename: Gaohui
authors.initials: G
authors.lastname: Zhu
authors.affiliation: Molecular Oncology Laboratory, Department of Surgery, The University of Chicago Medical Center, Chicago, IL 60637, USA; Stem Cell Biology and Therapy Laboratory, The Children's Hospital of Chongqing Medical University, Chongqing 400014, China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Luo
authors.affiliation: Molecular Oncology Laboratory, Department of Surgery, The University of Chicago Medical Center, Chicago, IL 60637, USA; Stem Cell Biology and Therapy Laboratory, The Children's Hospital of Chongqing Medical University, Chongqing 400014, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Bi
authors.affiliation: Molecular Oncology Laboratory, Department of Surgery, The University of Chicago Medical Center, Chicago, IL 60637, USA.
authors.forename: Stephanie H
authors.initials: SH
authors.lastname: Kim
authors.affiliation: Molecular Oncology Laboratory, Department of Surgery, The University of Chicago Medical Center, Chicago, IL 60637, USA; Key Laboratory of Diagnostic Medicine designated by Chinese Ministry of Education and Affiliated Hospitals, Chongqing Medical University, Chongqing 400016, China.
authors.forename: Jian-Li
authors.initials: JL
authors.lastname: Gao
authors.affiliation: Molecular Oncology Laboratory, Department of Surgery, The University of Chicago Medical Center, Chicago, IL 60637, USA; School of Bioengineering, Chongqing University, Chongqing 400044, China.
authors.forename: Enyi
authors.initials: E
authors.lastname: Huang
authors.affiliation: Molecular Oncology Laboratory, Department of Surgery, The University of Chicago Medical Center, Chicago, IL 60637, USA; Department of Cell Biology, The Third Military Medical University, Chongqing 400030, China.
authors.forename: Ke
authors.initials: K
authors.lastname: Yang
authors.affiliation: Molecular Oncology Laboratory, Department of Surgery, The University of Chicago Medical Center, Chicago, IL 60637, USA.
authors.forename: Linyuan
authors.initials: L
authors.lastname: Wang
authors.affiliation: Molecular Oncology Laboratory, Department of Surgery, The University of Chicago Medical Center, Chicago, IL 60637, USA; Stem Cell Biology and Therapy Laboratory, The Children's Hospital of Chongqing Medical University, Chongqing 400014, China.
authors.forename: Xing
authors.initials: X
authors.lastname: Liu
authors.affiliation: Molecular Oncology Laboratory, Department of Surgery, The University of Chicago Medical Center, Chicago, IL 60637, USA; Stem Cell Biology and Therapy Laboratory, The Children's Hospital of Chongqing Medical University, Chongqing 400014, China.
authors.forename: Mi
authors.initials: M
authors.lastname: Li
authors.affiliation: Molecular Oncology Laboratory, Department of Surgery, The University of Chicago Medical Center, Chicago, IL 60637, USA; Key Laboratory of Diagnostic Medicine designated by Chinese Ministry of Education and Affiliated Hospitals, Chongqing Medical University, Chongqing 400016, China.
authors.forename: Ning
authors.initials: N
authors.lastname: Hu
authors.affiliation: Molecular Oncology Laboratory, Department of Surgery, The University of Chicago Medical Center, Chicago, IL 60637, USA; Stem Cell Biology and Therapy Laboratory, The Children's Hospital of Chongqing Medical University, Chongqing 400014, China.
authors.forename: Yuxi
authors.initials: Y
authors.lastname: Su
authors.affiliation: Molecular Oncology Laboratory, Department of Surgery, The University of Chicago Medical Center, Chicago, IL 60637, USA; Key Laboratory of Diagnostic Medicine designated by Chinese Ministry of Education and Affiliated Hospitals, Chongqing Medical University, Chongqing 400016, China.
authors.forename: Xiaoji
authors.initials: X
authors.lastname: Luo
authors.affiliation: Molecular Oncology Laboratory, Department of Surgery, The University of Chicago Medical Center, Chicago, IL 60637, USA; Key Laboratory of Diagnostic Medicine designated by Chinese Ministry of Education and Affiliated Hospitals, Chongqing Medical University, Chongqing 400016, China.
authors.forename: Liang
authors.initials: L
authors.lastname: Chen
authors.affiliation: Molecular Oncology Laboratory, Department of Surgery, The University of Chicago Medical Center, Chicago, IL 60637, USA; Key Laboratory of Diagnostic Medicine designated by Chinese Ministry of Education and Affiliated Hospitals, Chongqing Medical University, Chongqing 400016, China.
authors.forename: Jinyong
authors.initials: J
authors.lastname: Luo
authors.affiliation: Molecular Oncology Laboratory, Department of Surgery, The University of Chicago Medical Center, Chicago, IL 60637, USA.
authors.forename: Rex C
authors.initials: RC
authors.lastname: Haydon
authors.affiliation: Molecular Oncology Laboratory, Department of Surgery, The University of Chicago Medical Center, Chicago, IL 60637, USA.
authors.forename: Hue H
authors.initials: HH
authors.lastname: Luu
authors.affiliation: Molecular Oncology Laboratory, Department of Surgery, The University of Chicago Medical Center, Chicago, IL 60637, USA; Key Laboratory of Diagnostic Medicine designated by Chinese Ministry of Education and Affiliated Hospitals, Chongqing Medical University, Chongqing 400016, China.
authors.forename: Lan
authors.initials: L
authors.lastname: Zhou
authors.affiliation: Molecular Oncology Laboratory, Department of Surgery, The University of Chicago Medical Center, Chicago, IL 60637, USA; Stem Cell Biology and Therapy Laboratory, The Children's Hospital of Chongqing Medical University, Chongqing 400014, China; Key Laboratory of Diagnostic Medicine designated by Chinese Ministry of Education and Affiliated Hospitals, Chongqing Medical University, Chongqing 400016, China.
authors.forename: Tong-Chuan
authors.initials: TC
authors.lastname: He
keywords: Mesenchymal stem cells; Osteosarcoma; Sarcomas; differentiation therapy; lineage-specific differentiation; sarcomagenesis; soft tissue tumors; tumorigenesis