Researchers from the Royal Marsden (RM) NHS FT, and the University College London Hospitals (UCLH) NHS FT, have discovered that cells from different parts of kidney tumours behave differently than cells within the centre of a tumour, and the cells in the centre have the highest chance of spreading.
The fact that cancers can spread to other parts of the body - with cells taking hold as secondary tumours - makes the disease much harder to treat. Understanding the mechanics of the spread (often referred to as metastasis) could lead to new treatments that stop this.
In their multidisciplinary study Nature Ecology and Evolution, scientists analysed 756 cancer biopsy samples from different parts of the body where tumours were, from the TRACERx Renal study.
They found that cells in the centre of tumours have a less stable genome and a higher potential to spread around the body. In contrast, cells on the tumour edge had lower rates of metastasis, as well as lower rates of growth and genetic damage.
Kevin Litchfield, paper author and Group Leader at the UCLH Cancer Institute, said: “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.”
The study demonstrates a need for awareness around the tumour centre to understand how cancer spreads, and to find the cancer cells at greatest risk to the patient. It also highlights the importance of developing treatments targeting the unique environmental conditions within the tumour core, in order to successfully remove the most aggressive tumour cells.
Researchers also looked at how genetically different populations of cancer cells grew within a tumour. They found that by using a unique map building tool to reconstruct the growth of tumour cells, two cases demonstrated a ‘jumping’ pattern where cells took hold in a new region of the tumour, by ‘jumping’ over other populations of tumour cells.
Samra Turajlic, Consultant Medical Oncologist at the RM, Head of the Crick’s Cancer Dynamics Laboratory, and the Chief Investigator of TRACERx study, 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 makeup 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 modelling, 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.”
The researchers now plan to reconstruct 3D tumour maps, which will provide an even clearer visualisation of the spatial patterns within tumours.