WP9 – Synaptic input to brain tumors in humans – potential implications for tumor growth, epilepsy and cancer treatment

Rationale

Recently, animal studies have indicated that tumor xenografts implanted into animal brains exhibit synaptic communication with neurons. Evidence suggests that these synapses play important roles in development of epilepsy and tumor growth. In-situ validation in human cancer patients has not yet been performed and is crucial to understand the mechanisms of action and the relevance of the observation. 

Objective

With this project we aim to

• provide the first evidence to date of neuron-to-braintumor-synapses in living human tissue specimens from brain cancer patients.
• validate recent findings from animal experiments suggesting a vicious cellular interaction between neurons and cancer cells, that facilitate tumor growth and stimulate neuronal hyperactivity.
• investigate the involvement of AMPA, NMDA, and GABAergic receptors in neuron-to-brain tumor signal transmission.

Approach

We will collect living tissue samples from brain cancer patients during neurosurgical procedures. Specimens will include braintissue and cancer tissue in one sample. The samples will be cultured and transfected with receptor specific fluorescent markers, but also investigated acutely with electrophysiological techniques, such as patch clamp methods, and molecularbiological techniques.

Endpoints

Characteristics of inhibitory and excitatory synaptic potentials (IPSCs and EPSCs)Expression patterns of growth factors and oncogenic proteins.

Expected impact

We expect the project will validate recent indications of biological interaction between neurons and tumor cells. This could potentially open new avenues of anti-cancer therapies and shed important light on tumor the mechanisms of tumor-induced epilepsy.