Abstract B14: A restricted cell population propagates MPNST growth after treatment

Abstract

Abstract Malignant peripheral nerve sheath tumor is a type of soft-tissue sarcoma that arises from the neural crest lineage and is commonly associated with nerve trunks. Surgical removal is the major treatment conjugated with chemo/radiation therapy when applicable. However, the complete tumor clearance is limited by the resectability, especially when tumor is associated with large peripheral nerve such as sciatic nerve, brachial plexus, and sacral plexus. The local recurrence of MPNST is 40-45% and distal recurrence is 40-48%. By harnessing our Nes-hsvTK-GFP transgene that successfully labeled the cancer stem cells in glioblastoma, we identified a small quiescent cell population in MPNSTs from both cisNf1+/-;Trp53+/- (cisNP) spontaneous model and skin progenitor (SKP)-based allograft model. Inhibition of these cells by feeding mice ganciclovir chow significantly decreased the tumor growth in both cisNP model and allograft model. We also found that the transgene-labeled GFP+ cells enrich in the sciatic nerve region compared to the distal tumor mass in MPNST allograft model. Tumor primary culture from the sciatic nerve vicinity forms significantly larger and more spheres in vitro than the distal tumor mass. The BrdU-EdU sequential labeling assay after chemotherapy in MPNST allograft model shows that the GFP+ cells can continuously repopulate tumor. These results indicate that the transgene-labeled GFP+ cells may serve as a source of tumor growth and, at the same time, a novel target to reduce MPNST relapse after treatment. Citation Format: Daochun Sun, Luis Parada. A restricted cell population propagates MPNST growth after treatment [abstract]. In: Proceedings of the AACR Conference on Advances in Sarcomas: From Basic Science to Clinical Translation; May 16-19, 2017; Philadelphia, PA. Philadelphia (PA): AACR; Clin Cancer Res 2018;24(2_Suppl):Abstract nr B14.