Astrocytes, the rising stars of the glioblastoma microenvironment

Abstract

Glioblastoma (GBM) is an aggressive primary tumor, causing thousands of deaths worldwide every year. The mean survival of patients with GBM remains below 20 months despite current available therapies. GBM cells' interactions with their stromal counterparts are crucial for tumor development. Astrocytes are glial cells that comprise ~50% of all brain cells and are therefore likely to establish direct contact with GBM cells. As other tumor cell types can hijack fibroblasts or immune cells to facilitate tumor growth, GBM cells can actually activate astrocytes, namely, the tumor associated astrocytes (TAAs), to promote GBM invasion in the healthy tissue. TAAs have thus been shown to be involved in GBM cells growth and limited response to radiation or chemotherapy (i.e., Temozolomide). Nevertheless, even though the interest in the cancer research community is increasing, the role of TAAs during GBM development is still overlooked. Yet, obtaining an in-depth understanding of the mechanisms by which TAAs influence GBM progression might lead to the development of new therapeutic strategies. This article therefore reports the different levels of GBM progression at which TAAs have been recently described to be involved in, including tumor cells' proliferation/invasion and resistance to therapies, especially through the activity of extracellular vesicles.

Keywords: brain; glioblastoma; stromal cells; tumor associated astrocytes; tumor microenvironment.