Mesenchymal Progenitors Expressing TRAIL Induce Apoptosis in Sarcomas

• DOI: 10.1002/stem.1903
• Publication Date: 2014-11-25T06:26:57Z
• Authors: Giulia Grisendi; Carlotta Spano; Naomi D'souza; Valeria Rasini; Elena Veronesi; Malvina Prapa; Tiziana Petrachi; Serena Piccinno; Filippo Rossignoli; Jorge S. Burns; Stefania Fiorcari; Donatella Granchi; Nicola Baldini; Edwin M. Horwitz; Valentina Guarneri; Pierfranco Conte; Paolo Paolucci; Massimo Dominici
• Keywords: Ewing's sarcoma

Sarcomas are frequent tumors in children and young adults that, despite a relative chemo-sensitivity, show high relapse rates with up to 80% of metastatic patients dying 5 years from diagnosis. The real ontogeny sarcomas is still debated evidences suggest they may derive precursors identified within mesenchymal stromal/stem cells (MSC) fractions. Recent studies on sarcoma microenvironment additionally indicated that MSC could take active part generation supportive stroma. Based this knowledge, we conceived use modified deliver tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) targeting different histotypes. Gene expressing TRAIL were cocultured osteosarcoma, rhabdomyosarcoma, Ewing's Sarcoma (ES) cell lines assessing viability caspase-8 activation. An vivo model focused ES was then implemented considering the impact MSC-TRAIL size, apoptosis, angiogenesis. induced significantly apoptosis all tested lines. death specifically associated activation starting 8 hours coculture MSC-TRAIL. When injected into pre-established xenotransplants, persisted its stroma, causing significant versus control groups. Additional histological vitro reveal also exert potent antiangiogenic functions. Our results as vehicles open novel therapeutic opportunities for by multiple mechanisms.