Glioma Exosomes and Astrocytes: Conversion to the Dark Side
Michael Graner, Professor, University of Colorado Anschutz School of Medicine
Glioblastomas (GBMs, WHO grade IV astrocytomas) are the worst of the
central nervous system tumors; despite maximum (and damaging)
therapeutic intervention, median survival time for patients is <15
months, and overall quality of life is poor. These abysmal outcomes have
changed little in 20 years. Clearly, our current therapies are
inadequate; we need innovative strides in understanding GBM biology to
rectify this situation. One “hot” research area is that of the impact of
tumor extracellular vesicles (EVs) on normal recipient cells. Tumor EVs
have extraordinary abilities to manipulate tumor microenvironments and
recipient cells both proximally and distally. Tumor EVs prepare the
“metastatic niche” for circulating tumor cells prior to colonization of a
target organ, deflect immune responses, and alter normal cells. Thus,
tumor EVs impact recipient cells to support tumor growth and
progression, which undoubtedly holds true for GBMs as well. However,
little is known about effects of GBM EVs on normal astrocytes—do GBM EVs
drive astrocyte phenotypic changes, potentially making the astrocytes
into tumor promotors? The answers could re-shape our paradigms on
gliomagenesis, particularly for recurrent tumors. Here we show that GBM
EVs activate cancer-type signaling pathways in recipient astrocytes,
promoting astrocyte migration towards the EVs, as well as astrocyte
anchorage-independent growth in soft agar. Astrocytes release of various
factors to generate a tumor-promoting milieu with increased tumor cell
growth, particularly in the areas of inflammatory responses to entities
that seem like viruses. We discuss the consequences of these phenomena
in the context of our current therapies with a view towards therapeutic
improvement.
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