Mobile Menu

Evolutionary arms race: artificial selection for host resistance to tumour growth

Researchers have used artificial selection to observe the evolutionary arms race between tumour cells and the host immune response.

Evolutionary arms race

Typically, cancer comprises of heterogenous cellular subpopulations that compete and interact with each other and their environment. The cells that are the fittest are optimally adapted to their local environmental conditions and so will proliferate. As tumour populations die with the host, they must find new strategies to overcome the host’s defences. Simultaneously, host species also evolve strategies to try and suppress cancer growth. Researchers refer to these competing dynamics as an ‘evolutionary arms race’.

Evolution can be driven by human or artificial selection through a series of intentional breeding for desirable traits. Human intervention, such as antibiotics, can also exert unintentional selection on organisms.

Artificial selection

In a study, published in British Journal of Cancer, researchers hypothesised that with appropriate selection forces, laboratory animals could evolve phenotypes that are resistant to the growth of implanted tumours. They hoped that this would provide insight into available tumour-suppression strategies. To achieve this, the team examined intentional bred immunodeficient SCID and immunocompetent Black/6 mice to evolve increased tumour suppression. Over 10 generations, they injected mouse lung carcinoma cells and selectively bred the two mice with the slowest tumour growth at day 11. Their male progeny were then hosts in the subsequent round.

Within 10 generations, both immunodeficient SCID and immunocompetent Black/6 mice were able to evolve tumour-suppressor adaptations to lung cancer cell tumours. Early suppression in the Black/6 mice depended on changes to the innate immune system. Whereas, the SCID mice suppressed tumour growth through biomechanical restriction from increased mesenchymal proliferation.

However, the researchers found that the tumour population deployed adaptive strategies through increased matrix remodelling in SCID mice and reduced angiogenesis, increased energy utilisation and accelerated proliferation in Black/6 mice.

Conclusion

Both immunocompetent and immunosuppressed mice evolved mechanisms to suppress tumour growth. Nonetheless, cancer cells eventually found adaptive strategies to overcome these suppression mechanisms, despite never previously encountering them. This interplay is key to understanding tumour evolution and can provide insight into how cancer cells adapt to evade the immune response. This, in turn, may be important for understanding therapeutic resistance.

Image credit: By freepik – www.freepik.com


More on these topics

Cancer / Cancer Research / Resistance / Tumour