Antiangiogenic Variant of TSP-1 Targets Tumor Cells in Glioblastomas

• DOI: 10.1038/mt.2014.214
• Publication Date: 2014-10-31T12:18:14Z
• Authors: Sung Hugh Choi; Kaoru Tamura; Rajiv Kumar Khajuria; Deepak Bhere; Irina Nesterenko; Jack Lawler; Khalid Shah
• Keywords: Thrombospondin 1; Brain tumor

Three type-1 repeat (3TSR) domain of thrombospondin-1 is known to have anti-angiogenic effects by targeting tumor-associated endothelial cells, but its effect on tumor cells unknown. This study explored the potential 3TSR target glioblastoma (GBM) in vitro and vivo. We show that upregulates death receptor (DR) 4/5 expression a CD36-dependent manner primes resistant GBMs necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced caspase-8/3/7 mediated apoptosis. engineered human mesenchymal stem (MSC) for on-site delivery potent secretable variant TRAIL (S-TRAIL) an effort simultaneously associated circumvent issues systemic drugs across blood-brain barrier. MSC-3TSR/S-TRAIL inhibits growth expanded spectrum GBMs. In vivo, single administration significantly targets both vascular component GBMs, progression, extends survival mice bearing highly vascularized GBM. The ability 3TSR/S-TRAIL act offers great broad cancers translate 3TSR/TRAIL therapies into clinics.