Predictable Characteristics Developed by Tumour Cells are not Random
Researchers at the Moffitt Cancer Center used a mathematical model to show that cells in the exterior and interior of a tumour develop different predictable characteristics.
Tumours are composed of many sub-populations of cells, and until now, the general consensus among scientists was that these sub-populations are due to random mutations.
This latest research by Moffitt Cancer Center, however, according to a new article entitled Darwinian Dynamics of Intratumoral Heterogeneity: Not Solely Random Mutations but Also Variable Environmental Selection Forces, published in the journal Cancer Research, seems to contradict this.
According to the researchers, certain sub-populations can be predicted and do not develop randomly as previously thought.
The Integrated Mathematical Oncology Department at Moffitt makes use of novel approaches and techniques to study cancer, and has developed a mathematical model based on evolutionary theories to show differences in sub-populations of tumours.
Their model is based on the evolutionary concept that, similar to all living organisms, cancer cells can invest resources in reproduction or the ability to survive, but not both.
This has led researchers, using the above model, to the discovery that cancer cells that are situated at the edge of a tumour, close to the surrounding environment are predictably different from the cells within the interior of the tumour. Cells at the edge of a tumour invest their limited resources into cellular characteristics that promote invasion and the ability to use resources from the surrounding environment, such as blood vessels. Exterior cells develop these characteristics despite their association with a higher risk of cell death.
Cancer cells within the interior of a tumour however, are surrounded by many other cells and are farther away from the resources present within the environment. Interior cells therefore develop characteristics that allow them to compete with neighbouring cells for the limited resources available to them.
Data from the research was confirmed by showing that cells within the interior and exterior of breast cancer tissue display distinct gene expression patterns:
- Cells within the interior of a tumour have characteristics that are more static, including less proliferation and more cell death;
- Cells around the exterior of a tumour have higher rates of proliferation and are more likely to be producing an acidic environment, which is consistent with the need for cells on the edge of a tumor to grow and invade into the surrounding normal tissue.
Robert A. Gatenby, M.D., senior member and chair of the Department of Diagnostic Imaging and Interventional Radiology at Moffitt said:
“Interestingly, differences within a single population are seen in biological invasions in nature. For example, the cane toad has been invading Australia for many years. The cane toads at the edge of the invasion have bigger legs presumably because they are adapted to moving farther and faster. However, the characteristics of the invading cane toads that have allowed them to move farther and faster also come with a price: severe spinal arthritis is found in 10% of the larger-legged toads.”
The Moffitt researchers hope that by understanding the characteristics of invading tumour cells that it may be possible to find and target their Achilles heel to promote the evolution of non-invasive characteristics and slow tumour growth.