Cancer cells ‘corrupt’ their healthy neighbours

Cancer cells corrupt their healthy neighbours in order to support their own survival, scientists say.

The discovery was made using a new state-of-the-art technique to study the tissue around a tumour – called the tumour microenvironment – known to influence the growth and spread of cancer, as well as treatment response.

Dr Ilaria Malanchi at the Francis Crick Institute, who joint-led the project, said: “Our new technique allows us to study changes to cells in the tumour microenvironment with unprecedented precision.

“This helps us to understand how these changes relate to tumour growth and metastasis, allowing us to develop better strategies to treat the disease.

“We discovered that non-cancerous cells in the tumour microenvironment regress back into a stem-cell like state, and actually support cancer growth.

“By corrupting its neighbours, cancer transforms its local environment to support its own survival.”

The new technique relies on cancer cells engineered to release a cell-penetrating fluorescent protein that gets taken up by its neighbouring cells.

These can then be identified and compared to unlabelled cells that have not come into contact with the tumour.

In the study published in Nature, researchers used this approach in mice to analyse the cells around breast cancer that had spread to the lungs.

Data from Alessandro Ori’s lab at the Fritz Lipmann Institute in Germany confirmed that the labelled cells produced different proteins to unlabelled cells.

Scientists found labelled cells from the lung to have stem cell-like features, unlike the lung cells found outside of the tumour microenvironment.

The team showed those cells from the mouse lungs supported tumour growth when mixed with tumour cells in 3D culture in the lab, suggesting that they help the cancer to survive and grow.

To further test the potential of the stem-cell like cells in the tumour microenvironment, Dr Malanchi teamed up with Joo-Hyeon Lee at the Wellcome-MRC Stem Cell Institute who used them to grow lung organoids, or “mini-lungs”.

They found the unlabelled healthy lung cells formed mini-lungs, mostly made up of alveolar epithelial cells which line the lung’s alveoli – the tiny sacs where gas exchange takes place.

But the labelled cells taken from the tumour microenvironment unexpectedly formed mini-lungs with a wider range of cell types.

“To our amazement, we found that cells receiving proteins from adjacent cancer cells obtained stem-cell-like features,” said Joo-Hyeon Lee, joint senior author of the paper.

She added: “They could change their fate to become different cell types.

“It demonstrates the powerful influence that cancer exerts over its neighbouring cells, making them liable to change easily.”

It is hoped the approach will be used by other scientists looking to gain a deeper understanding of the local changes triggered by cancer which help it to survive, spread and develop resistance to treatments.

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