生物医学

研究课题：用于了解脑部癌症生长和侵袭分子机理基础的神经胶质瘤斑马鱼模型研究

A glioblastoma zebrafish model to understand the molecular mechanisms underpinning the growth an d invasiveness of brain cancers

Introduction

Glioblastoma multiforme is the most common an d deadliest form of brain cancer an d is highly resistant to therapeutic strategies. Glioblastomas are known to contain a high number of microglia/macrophages. This microglial/macrophage invasion supports tumour growth an d the infiltration of surrounding brain tissue by glioma cells. Importantly, the presence of macrophages/microglia positively correlates with glioma grade an d prognosis. However, the exact nature of microglia/macrophage-glioma interactions is not well understood but our experimental design provides a unique opportunity to study the cellular an d molecular mechanisms that promote malignant glioma growth.

In this project we will establish the first zebrafish model in Australia to study glioblastoma growth an d invasiveness in real-time in the living brain. Our team has established a collaboration with the University of Edinburgh to study microglia-brain tumour cell interactions in vivo in the larval zebrafish brain. We will be using state-of-the-art fluorescent labelling an d visualisation techniques that allow us to track tumour progression an d the impact of microglia to regulate that process. Targeting these microglia interactions may provide future therapeutic interventions to delay Ｏr even halt the progression of the tumour. In addition, our experimental system will provide unique insights into how microglia precursors may be used as a non-invasive route of access to the brain.

Hypothesis

Microglia an d macrophages that have colonised the glioblastoma display pro-tumoral characteristics an d interfering with the activation profile of these cells may delay tumour progression.

Aims

Aim 1: Investigate how host zebrafish microglia respond to the transplantation of human glioblastoma cells into the zebrafish brain.

Aim 2: Assess how microglia interference can affect tumour growth an d invasiveness in vivo.

Aim 3: Test if microglia infiltration can be utilised to deliver therapeutic cargo （payload） directly to the tumour cells.

Outcome

We will establish the first glioblastoma model in zebrafish in Australia to test how microglia interact with human brain cancer cell lines. We hypothesize that manipulating microglia-tumour interactions will affect tumour progression. Understanding microglia-glioblastoma interactions will provide important insights into glioblastoma pathogenesis.