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A Three-Dimensional Tumour Model Replicates Oxygen Starvation in Cancers

last modified Dec 03, 2015 10:31 AM

November 2015

- Dr. Christian Frezza is the lead author from the MRC Cancer Unit on a recently published paper in Nature Materials, which describes the development of the first 3D tumour model to investigate how cancers adapt to low levels of oxygen. The following report has been adapted from a recent press release of the manuscript.

 

Scientists from the MRC Cancer Unit, working with researchers at the University of Toronto, have developed the first 3D model of a tumour to study how cancers can survive with low levels of oxygen. The model is a tissue-engineered platform, termed the Tissue Roll for Analysis of Cellular Environment and Response (TRACER).

It allows human cells to be cultured in a 3D-relevant environment (below left), in combination with the capacity to analyse variations in cell properties within the model. Such a tool will reveal more about the inner workings of cancers and help the development of new treatments.

This 3D model was created by coating a thin surface with cancer cells, then rolling this around a cylindrical core to create an environment (3D layered structure), where the innermost cells are deprived of oxygen. This establishes an oxygen gradient that mimics the same situation found within a tumour in the body. The researchers were then able to glimpse into the world of the tumour by rapidly unwinding the scaffold (below right).

Left: Photo of series of rollable tumours in a dish. Right: Thin strip containing cancer cells. [Please click image for video]

Photo of series of rollable tumours in a dish. Thin strip containing cancer cells. [Please click for video]

This revealed how the amount of oxygen varied within the tumour, and the implications this has on cell growth and treatment response.

The researchers were also able to reveal the metabolic responses cancer cells make to survive in a low oxygen environment.

3dtumourmodel3
Imaging of stacked layers to measure oxygen levels through engineered tumour.
The lack of oxygen within a tumour is often down to the creation of new blood vessels lagging behind the cancers growth. To adapt to this, cells change their metabolic behaviour to cope, including their use of oxygen, to ensure continued growth and survival.

This response is controlled by a number of pathways so that some oxygen is able to permeate all the way through the tumour, ensuring that no cells die because they are completely starved of oxygen.

The 3D tumours also replicated a cancer’s response to treatment – levels of the common chemotherapy drug doxorubicin plateaued deeper into the tumour. The response to radiotherapy was also similar to that seen in humans where cells with low oxygen were less likely to die. 

3dtumourmodel4
Cellular organization in the engineered tumour.


Dr Christian Frezza, the lead researcher from the MRC Cancer Unit, said: “Cancers grow rapidly, and to support this growth, cells need to be able adapt in an environment where the supply of oxygen can’t keep up. While this phenomenon has been known for some time, gaining an experimental insight to the metabolic processes that the cells use to survive has proved a challenge.”

“Our new model allows us to look at cellular metabolism in 3D to investigate how a tumour response to low oxygen is tightly controlled, and how cells are unable to adapt and survive without this control. This knowledge could lead to the development of new treatments that target these oxygen deprived cancer cells, which can be the hardest to target and destroy.”

 

The study is published in Nature Materials.

TedXUofT talk on paper by AP McGuigan