Review: Glioblastoma and Astrocytes Interactions, Mediated by Extracellular Vesicles, Affects Tumor Progression
Key findings
- Astrocytes protect neurons at an early stage in the development of glioblastoma, but as the tumor develops, astrocytes seem to lose their protective role and become pro-tumorigenic
- One way astrocytes and glioblastoma cells interact is through secretion of extracellular vesicles (EVs) by both types of cells
- When astrocytes take up glioblastoma-derived EVs, they gain increased ability to break down the tumor extracellular matrix, which is important for tumor growth and invasion
- To further support the tumor, reactive astrocytes create a favorable immune environment; moreover, glioblastoma-derived EVs can drive astrocyte progenitors to take on properties of glioblastoma cells
- Better understanding of EV exchange may pave the way for novel glioblastoma therapies such as by suppressing specific EV-mediated communication or using EVs to deliver therapeutic agents to tumors
The cellular microenvironment around a tumor is now known to contribute to its aggressiveness. Glioblastoma is a heterogeneous tumor, with astrocytes as the most abundant cell type, which initially form a border around the tumor to protect non-tumor cells from invasion. However, over time, at least some of these antitumorigenic astrocytes become tumor-supportive.
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One way astrocytes and glioblastoma cells communicate is through the secretion of extracellular vesicles (EVs) by both types of cells. In Trends in Neurosciences, graduate student researcher Lisa Nieland, Xandra O. Breakefield, PhD, investigator in Neurology at the Mass General Research Institute, and Erik R. Abels, graduate student researcher, of the Department of Neurology and Department Radiology at Massachusetts General Hospital, and colleagues review how EV-mediated crosstalk between astrocytes and tumor cells is thought to contribute to glioblastoma development.
Background on EVs
EVs are membrane-enclosed nanospheres, released by most cells, that contain proteins, lipids and nucleic acids. The EV-mediated communication pathway is unique in that it allows the delivery of its protected "cargo" to neighboring cells and to distant sites.
Evidence suggests the content of glioblastoma-derived EVs mirrors the phenotypic and genotypic signature of the respective glioblastoma cells, at least to some extent. Glioblastoma-derived EVs can be taken up by different cells in the tumor environment, including astrocytes.
Effects of Glioblastoma-derived EVs on Astrocytes
In response to glioblastoma development, astrocytes become reactive. To further support the tumor, reactive astrocytes create a favorable immune environment. Astrocytes take up glioblastoma-derived EVs, which contain factors that contribute to the break-down of the extracellular matrix, important for tumor growth and invasion.
An article in Neuro-Oncology reported that temozolomide, a chemotherapy commonly prescribed for glioblastoma, alters the composition of EVs shed by tumor cells. Whether this produces a pro- or antitumorigenic change in astrocytes is still unknown.
Effects of Astrocyte-derived EVs on Glioblastoma
A growing body of evidence indicates that astrocytes release EVs to transfer information. A cell culture study published in Nature showed that astrocyte-derived EVs decrease levels of the tumor suppressor gene PTEN in tumor cells.
Therapeutic Implications
A better understanding of EV exchange between astrocytes and tumor cells may pave the way for therapies that wrest control of the tumor microenvironment from glioblastoma cells. For example, there may be ways to suppress specific EV-mediated communication. Another possibility is that EVs themselves could be loaded with therapeutic agents for delivery to tumors.
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