Cancer becomes most deadly when it has metastasized - when cancerous cells move away from the site where cancer started growing and into the lymphatic system or bloodstream, which generates new tumors in other places. It has been estimated that 90 percent of cancer deaths are due to metastasis. Now researchers have learned more about how metastatic cancer cells choose their path.
Reporting in Nature Communications, the scientists report that metastatic cancer cells may move quickly, but they're lazy in selecting their route. They pick their path based on how much energy will be required; they opt for wider spaces that are easy to navigate over tight, confined spaces, which reduces the amount of energy it takes to get through.
The work suggests that metabolism and energy are crucial factors during metastatic movement. It may further raise research interest in cellular metabolism as factors in cancer, and make metabolomics a bigger target in the prevention of metastasis.
This study, led by Cornelius Vanderbilt Professor of Engineering Cynthia Reinhart-King of Vanderbilt University, is the first to quantify the energy that cancer cells use during metastasis, which can help predict the path of migration. It builds on previous work by the Reinhart-King lab that identified tools that cancer cells use as they migrate. These cells act like a car driver trying to save gas, by drafting behind other cells. The cells in the front use more energy as they carve a path and the ones in the back don't need as much energy. When the ones in front are worn out, cells in the rear can move ahead and take on a bigger workload.
"These cells are lazy. They want to move, but they will find the easiest way to do it," explained Reinhart-King. "By manipulating many different variables, we were able to track and build predictions of cellular preference for these paths of least resistance in the body based on how much energy a cell would need to move."
In this study, the cellular movement of cancer cells was tracked through a maze, and graduate student and lead study author Matthew Zanotelli tinkered with the properties of the paths and the mechanical characteristics of the cells. Although their focus was metastatic cancer cells, this research may have broader impact, he noted.
"This type of cellular movement happens in other instances, for example, during inflammation and around healing wounds," said Zanotelli. "We're excited to have this initial understanding of energy and cell migration and hope it will prove foundational for future, broader research."