Senescence bypass in mesenchymal stem cells: a potential pathogenesis and implications of pro-senescence therapy in sarcomas

Abstract

Cellular senescence is a mechanism that limits the lifespan of somatic cells as the results of replicative proliferation and response to stresses, and that prevents undesired oncogenic changes constituting a barrier against immortalization and tumorigenesis. Mesenchymal stem cells (MSCs) reside in a variety of tissues, and participates in tissue maintenance with their multipotent differentiation ability. MSCs are also considered to be as cells of origin for certain type of sarcomas. We reviewed the mechanisms of cellular senescence in MSCs and hypothesized senescence bypass as the potential pathogenesis for sarcoma development, and proposed the possibility of senescence induction therapy for an alternative treatment strategy against sarcomas, especially cells with the resistance to conventional chemo and radiotherapy including sarcoma stem cells.