Tmic-24. the contribution of vascular co-option and tumor-derived endothelial cells to gbm recurrence

Despite aggressive treatment, the prognosis for glioblastoma (GBM) is very poor. The rate of recurrence is nearly 100%, and the recurrent tumor is usually more aggressive and resistant to treatment. The presence of a small population of tumor-initiating cells, the glioma stem cells (GSCs), has been associated with tumor recurrence and resistance to further therapy. To understand the role of GSCs on recurrence, we performed gene expression analysis on human-derived GBM xenografts (PDX) in both primary and recurrent models in vivo. The analysis indicated 3 angiogenesis-associated genes in recurrent GBM samples: CD34, CD105, and SERPINB2. These markers are directly related to neo angiogenesis and migration of GBM cells. The use of an in vivo cranial window model allowed us to identify fluorescently labeled GBM cells in proximity to newly formed blood vessels in the recurrent model. Further analysis indicated that the labeled GBM cells expressed markers of progenitor and mature endothelial cells (ECs), both in vivo and in vitro. The GSC-specific reporter system showed that GSC populations also increase in the EC population after primary chemotherapy. The functionality of these newly formed ECs was demonstrated through tube formation assay and Dio-Ac-LDL uptake. In vivo and in vitro analysis of untreated PDX models did not show such increase in the GSC or EC population over time. Our results strongly suggest increased conversion of GSCs into ECs in the recurrent GBM model followin...
Source: Neuro-Oncology - Category: Cancer & Oncology Authors: Tags: TUMOR MICROENVIRONMENT Source Type: research