Neural precursor cells induce cell death of high-grade astrocytomas through stimulation of TRPV1.

Primary astrocytomas of grade 3 or 4 according to the classification system of
the World Health Organization (high-grade astrocytomas or HGAs) are preponderant among
adults and are almost invariably fatal despite the use of multimodal therapy. Here we
show that the juvenile brain has an endogenous defense mechanism against HGAs. Neural
precursor cells (NPCs) migrate to HGAs, reduce glioma expansion and prolong survival time
by releasing endovanilloids that activate the vanilloid receptor (transient receptor
potential vanilloid subfamily member-1 or TRPV1) on HGA cells. TRPV1 is highly expressed
in tumor and weakly expressed in tumor-free brain. TRPV1 stimulation triggers tumor cell
death through the branch of the endoplasmic reticulum stress pathway that is controlled
by activating transcription factor-3 (ATF3). The antitumorigenic response of NPCs is lost
with aging. NPC-mediated tumor suppression can be mimicked in the adult brain by systemic
administration of the synthetic vanilloid arvanil, suggesting that TRPV1 agonists have
potential as new HGA therapeutics.