Researchers have found that cells from different parts of kidney tumours behave differently, and cells within the centre of a tumour are the most aggressive and most likely to spread around the body.
Metastasis, where cancer cells from tumours spread to other parts of the body, is the main cause of death in cancer patients.
In this multidisciplinary study published in Nature Ecology and Evolution, scientists analysed 756 cancer biopsy samples from different regions within tumours from the TRACERx Renal study.
They discovered that, in contrast to the cells at the outside of tumours, the cells in the centres of tumours have more unstable genomes, and a higher potential for metastasis. The cells on the outside had lower growth rates and had less genetic damage.
“Cancer cells in the central zone of the tumour face harsh environmental conditions, as there’s a lack of blood supply and oxygen. They have to adapt to survive, which makes them stronger and more aggressive. This also means they are more likely to successfully evolve into cells that can disseminate and take hold in distant organs,” explained Kevin Litchfield, paper author and group leader at the UCL Cancer Institute.
These findings show that it is important to focus on the tumour centre for a better understanding of how cancer spreads, and identify the most dangerous cells. Also, in order to wipe out the most aggressive tumour cells, treatment development must target the unique environmental conditions found within the tumour core.
The scientists also examined how genetically different populations of cancer cells grow within a tumour. With a unique mapping tall that reconstructed the growth of tumour cells, they discovered that, while tumours tend to follow a pattern where populations of cells grow in the local area, in two cases, cells took hold in a new region of the tumour by seemingly ‘jumping’ over other populations of tumour cells.
For their next steps, the researchers aim to reconstruct 3D tumour maps, providing even better visualisation of the tumours’ internal structure.
Samra Turajlic, head of the Crick’s Cancer Dynamics Laboratory, Consultant Medical Oncologist at the Royal Marsden NHS Foundation Trust and the Chief Investigator of TRACERx Renal, said: “Cancer spread is one of the biggest barriers to improving survival rates. In the context of the TRACERx Renal study we previously resolved the genetic make up of different tumour areas, but until now, there has been no understanding of how these differences relate spatially. The most critical question is the part of the tumour from which cancer cells break away and migrate making cancer incurable.
“Using this unique clinical cohort and a multidisciplinary approach, including mathematical modeling, we identified with precision the place in the tumour where genetic chaos emerges to give rise to metastases. Our observations shed light on the sort of environmental conditions that would foster emergence of aggressive behaviour. These findings are a critical foundation for considering how we target or even prevent distinct populations of cells that pose the biggest threat.”
Source: Francis Crick Institute
