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Previously we described direct cellular interactions between microglia and AKT1+ brain tumour cells in zebrafish (Chia et al., 2018). However, it was unclear how these interactions were initiated: it was also not clear if they had an impact on the growth of tumour cells. Here, we show that neoplastic cells hijack mechanisms that are usually employed to direct microglial processes towards highly active neurons and injuries in the brain. We show that AKT1+ cells possess dynamically regulated high intracellular Ca 2+  levels. Using a combination of live imaging, genetic and pharmacological tools, we show that these Ca 2+  transients stimulate ATP-mediated interactions with microglia. Interfering with Ca 2+  levels, inhibiting ATP release and CRISPR-mediated mutation of the  p2ry12  locus abolishes these interactions. Finally, we show that reducing the number of microglial interactions significantly impairs the proliferation of neoplastic AKT1 cells. In conclusion, neoplastic cells repurpose the endogenous neuron to microglia signalling mechanism via P2ry12 activation to promote their own proliferation.

Brain tumours repurpose endogenous neuron to microglia signalling mechanisms to promote their own proliferation