Metastatic migration of cancer cells is not random, new evidence shows that cancer cells chose the path of least resistance when migrating, suggesting that energy expenditure and metabolism are key factors related to metastatic migration.
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These findings, that come from a team at Vanderbilt University, suggest that metastasis may be able to be prevented by targeting cellular metabolism.
The results from their new study, which were published last September in the journal, Nature Communications, adds to a growing body of research that is demonstrating the value of metabolomic study in oncology.
Metastasis remains the main cause of cancer-related deaths
Metastasis is a word that no one going through cancer treatment wants to hear. It is the number one cause of mortality in cancer, being attributed to around 90% of deaths.
While survival rates for cancer have shown great improvement over the past few decades, this is mostly related to the developments that have been made in early diagnosis and the success in improving systems to inhibit cancer growth.
In comparison, there has been limited progress made in the field of preventing metastasis. This is because of a number of factors, as metastasis is a complex process that encompasses a variety of interrelated steps and biochemical actions, many of which still need to be fully investigated to be thoroughly understood.
Current cancer treatments that target metastasis include chemotherapy and radiotherapy, as well as newer anti-cancer drugs. However, metastasis remains the leading cause of cancer-related death. Therefore, there is a call for new treatments to be developed that can effectively target metastasis.
Researchers at Vanderbilt University designed a study with the purpose of better understanding the nature of metastasis, observing how it decides on migration pathways, and determining which factors are essential to this process.
Cancerous cells migrate down the path of least resistance
The team, including lead its author, graduate student Matthew Zanotelli, employed several methods designed to observe and record the movement of cancer cells.
The researchers implemented complex designs, where they created a maze of pathways through which they tracked cells’ movements after altering each cell’s mechanical or physical properties, or the path itself.
The movements of the cells revealed something that had not been proven before. The team observed that the cells, while motivated to move, were lazy. It was noted that the cells were always looking for the easiest path to take, across all the different variables applied, cells consistently took the path of least resistance.
Energy consumption was determined as the major driving factor for this behavior, with cells predetermined to select pathways that would take the least amount of energy to move down.
Wider, and easier to maneuver paths were chosen over small, narrow paths that required large amounts of energy to traverse. Scientists concluded that because of this behavior, energy expenditure and metabolism are likely to be key factors that underly metastatic migration.
The team's conclusion of the involvement of these factors is supported by previous recent research projects that have increased the interest in using metabolomics to study cancer. Specifically, in the use of metabolomics to investigate metastasis.
The research, which was led by Cornelius Vanderbilt Professor of Engineering, Cynthia Reinhart-King, was the first study of its kind to investigate the energetic costs of cancer cells during the metastatic process.
The evidence presented by this study adds to research published earlier in 2019 from the Reinhart-King Lab, which demonstrated cancer cells using "drafting" techniques to reduce energy expenditure during migration.
Future cancer treatments may be impacted by the findings of this research and the research that will follow on from it. Hopefully, it will be instrumental in the development of new therapies that can more effectively target metastasis.
Also, scientists believe the findings have the potential to be applied to situations outside of the realm of oncology.
· Guan, X. (2015). Cancer metastases: challenges and opportunities. Acta Pharmaceutica Sinica B, 5(5), pp.402-418. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4629446/#!po=67.0000
· Zanotelli, M., Rahman-Zaman, A., VanderBurgh, J., Taufalele, P., Jain, A., Erickson, D., Bordeleau, F. and Reinhart-King, C. (2019). Energetic costs regulated by cell mechanics and confinement are predictive of migration path during decision-making. Nature Communications, 10(1). https://www.nature.com/articles/s41467-019-12155-z#citeas