Mapping glioblastoma cells 

Fast facts

• Official title: Mapping the spatio-temporal heterogeneity of glioblastoma invasion
• Lead researcher: Professor Simona Parrinello 
  
• Where: University College London
• When: September 2019 – February 2025
• Cost: £1,496,690 (supported by The Oli Hilsdon Foundation)
• Research type: Academic, Lab-based, Glioblastoma, Adult
• Grant round: Quest for Cures

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What is it?

Glioblastomas are diffuse in nature, meaning the tumour cells can spread through healthy parts of the brain. This is through a process called invasion, and makes it difficult to completely remove the tumour during surgery. Due to this, recurrence is a risk with glioblastomas as the tumour cells left behind can grow into a new tumour.

Professor Parrinello, and her colleagues at Imperial College London, aim to understand how glioblastomas spread into the brain and how they use small molecules as messengers to communicate with surrounding cells. It is likely that glioblastoma use different molecules to communicate with different types of cells, which makes identifying the various molecules difficult.

The multi-disciplinary research team will investigate this communication by combining both biological and mathematical principles and using two new techniques called spatial transcriptomics and intravital photoacoustic imaging (PAI).

Spatial transcriptomics is a technique that allows researchers to characterise different cells while preserving information about the cells’ original location.

Characterisation of the cells means that we will know what changes are present in cells at each location. If the changes vary in different areas of the tumour it gives us insight into how to develop more specific treatments.

PAI is an advanced imaging technique that uses light and sound to create high resolution images. The research team will use PAI to create images of the brain that will help them visualise the invasion of glioblastoma cells deep inside the brain.

These two techniques will allow the researchers to map the invasion process and identify key molecules that help the tumour cells spread. This understanding will help researchers develop more effective therapies that will help block tumour cells from spreading and prevent recurrence.

Why it is important?

Currently, not much is known about how a glioblastoma invades the surrounding brain because:

• tumour cells that spread deep into the brain cannot be studied easily
• there are considerable differences within a single tumour and between each person
• the brain is complex and contains many different types of cells in different regions of the brain.

These obstacles are some of the reasons that, even with the current gold standard of care, a glioblastoma diagnosis comes with a poor prognosis and, even after treatment, tumour recurrence is very likely.

This research project aims to address all these obstacles and help us find drug targets to prevent tumour recurrence. Giving people with a glioblastoma much-needed hope for a future where brain tumours are defeated.

Who it will help?

The researchers on this project have a broad range of interests and are coming together to fill a significant gap in our knowledge, namely ‘why do glioblastomas keep coming back?’

This work has the potential to benefit everyone who has had treatment for a glioblastoma and is living with the worry that it will return.

Milestones

Achieved

Study the different types and locations of the tumour edge and its surrounding areas

• Created 12 tumour cell samples from patients and used them to create tumours in mice.
• Examined 10 of these tumours using a method called Spatial Transcriptomics (ST).
• Discovered two main patterns of tumour spread and their molecular makeup and identified some molecules that are related to invasive behaviour (SOX9).

Study changes and variety at the tumour’s edge over time

• Found genes that can  show changes in tumour cell behaviour as they spread
• Worked on ways to see tumour cell location and brain structure in living tumours, including  one method that could be used in a clinical setting
• Developed methods to analyse MRI images to monitor tumour growth in living animals in real time
• Established techniques to make the brain transparent so they can see and study the tumours in 3D at the single cell level (brain clearing).

Find out how the variety at the tumour’s edge affects the way it spreads, focusing on white matter tract infiltration

• Discovered an important molecule (SOX9) that plays a role in the spreading of the tumour
• Created methods to study the spreading process in a lab setting and used these methods to study  the function of SOX9 before doing experiments with mice
• The team has analysed the spatial transcriptomics (ST) data from several GBM mouse models. This  is still ongoing but an interesting result has been that highly invasive tumours have features  of astrocyte cells (normal cells of the brain involved in normal neuronal function and brain repair) whereas more circumscribed tumours have properties of injured brain cells.

Upcoming

Focus for 2023/24

• Continue studying the two patterns of tumour spread and the molecules involved. They will look at how these behaviours respond to standard treatment and if there are differences in treatment resistance. They will also see if therapy changes the way tumours spread.
• Complete the study on MRI imaging of tumour spread and test the usefulness of the PAI reporters they have developed for imaging invasive behaviours. They will use their new brain-clearing method to see how the two invasive behaviours develop over time. They will combine this data with their computational models.
• Investigate the role of SOX9 and related molecules in driving tumour spread.

If you have any questions about this, or any of our other research projects, please contact us on [email protected]