New research stemming from a collaboration between researchers from the Francis Crick Institute, Royal Marsden, UCL and Cruces University Hospital shows that cells at the center of tumors are the most aggressive and are highly metastatic. The team has published their findings on the diverse behaviors of tumor cells based on tumor regionality in the journal Nature Ecology and Evolution.
In an analysis of 756 cancer biopsy samples from different regions within kidney tumors, the researchers observed a higher rate of metastasis in less genomically stable cells at the center of tumors, compared to cells at the edges of tumors. The team pulled their data from the TRACERx Renal study in order to investigate rates of growth and genetic damage based on cell location within a tumor.
"Cancer cells in the central zone of the tumor 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," explains study author Kevin Litchfield.
Understanding the spatial patterns and behaviors within tumors is key to developing precision medicine treatments that consider a patient’s specific tumor. In order to further their work, the team intends to reconstruct 3D tumor maps that allow them to visualize the ongoing processes inside of tumors.
"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 tumor areas, but until now, there has been no understanding of how these differences relate spatially. The most critical question is the part of the tumor from which cancer cells break away and migrate, making cancer incurable,” commented Chief Investigator of TRACERx Renal, Samra Turajlic.
"Using this unique clinical cohort and a multidisciplinary approach, including mathematical modeling, we identified with precision the place in the tumor where genetic chaos emerges to give rise to metastases. Our observations shed light on the sort of environmental conditions that would foster the emergence of aggressive behavior. These findings are a critical foundation for considering how we target or even prevent distinct populations of cells that pose the biggest threat."