Tmic-08. glioblastoma-induced astrocyte reprogramming generates a positive feedback loop to glioblastoma cells

Gliomas are lethal primary brain tumors inherently resistant to therapy. Several reports suggest a role for a stromal involvement in the progression of these tumors. We have previously isolated tumor associated astrocytes (TAGs) from mouse models of primary glioblastoma. We show for the first time that TAGs have a different gene expression profile from primary glial cells from mice without tumors. TAGs upregulate angiogenic factors and reprogramming factors like SOX2 and POU3F2 as well as Nestin and PDGFRa, normally expressed in neuronal precursors and oligodendrocyte precursors, respectively. Moreover, when isolated by FACS and reimplanted with tumor cells in mice, TAGs promoted tumor growth compared to control tumors co-injected primary glia from mice without tumors. In vitro experiments confirmed that tumor-secreted factors induce these transcriptional changes in human astrocytes, as conditioned media from primary glioblastoma biopsies lead to an upregulation of POU3F2, SOX2 and Nestin in a human astrocyte (HA) cell line. In addition, conditioned media from HA promoted growth and induced migration of glioblastoma cell lines. These data suggest an interplay between human astrocytes and glioblastoma cells, that could potentially work as a new therapeutic target. Current work aims at further investigating the expression profile and secretome of glioma cells and HAs grown in conditioned media from the other cell type, as well as elucidating mechanisms behind their tumor promot...
Source: Neuro-Oncology - Category: Cancer & Oncology Authors: Tags: TUMOR MICROENVIRONMENT Source Type: research