# Changes in adrenoceptor expression level contribute to the cellular plasticity of glioblastoma cells

## TL;DR

Glioblastoma cells change their adrenoceptor levels to adapt and survive, which could lead to new treatments.

## Contribution

The study reveals that adrenoceptor expression changes in glioblastoma cells affect their plasticity and prognosis.

## Key findings

- Glioblastoma cells alter adrenoreceptor expression based on their differentiation stage.
- Noradrenaline promotes stemness and dedifferentiation via α1D-adrenoreceptor signaling.
- High α1D-adrenoreceptor expression correlates with poor glioma patient outcomes.

## Abstract

Glioblastoma cells are known to regulate their cellular plasticity in response to their surrounding microenvironment, but it is not fully understood what factors contribute to the cells’ changing plasticity. Here, we found that glioblastoma cells alter the expression level of adrenoreceptors depending on their differentiation stage. Catecholamines are abundant in the central nervous system, and we found that noradrenaline, in particular, enhances the stemness of glioblastoma cells and promotes the dedifferentiation potential of already differentiated glioblastoma cells. Antagonist and RNAi experiments revealed that signaling through α1D-adrenoreceptor is important for noradrenaline action on glioblastoma cells. We also found that high α1D-adrenoreceptor expression was associated with poor prognosis in patients with gliomas. These data suggest that glioblastoma cells increase the expression level of their own adrenoreceptors to alter the surrounding tumor microenvironment favorably for survival. We believe that our findings will contribute to the development of new therapeutic strategies for glioblastoma.