Researchers Unpack a Cellular Traffic Jam As Used by Cancer
Gabriel Popkin reports in Quanta:
In 1995, while he was a graduate student at McGill University in Montreal, the biomedical scientist Peter Friedl saw something so startling it kept him awake for several nights. Coordinated groups of cancer cells he was growing in his adviser’s lab started moving through a network of fibers meant to mimic the spaces between cells in the human body.
For more than a century, scientists had known that individual cancer cells can metastasize, leaving a tumor and migrating through the bloodstream and lymph system to distant parts of the body. But no one had seen what Friedl had caught in his microscope: a phalanx of cancer cells moving as one. It was so new and strange that at first he had trouble getting it published. “It was rejected because the relevance [to metastasis] wasn’t clear,” he said. Friedl and his co-authors eventually published a short paper in the journal Cancer Research.
Two decades later, biologists have become increasingly convinced that mobile clusters of tumor cells, though rarer than individual circulating cells, are seeding many — perhaps most — of the deadly metastatic invasions that cause 90 percent of all cancer deaths. But it wasn’t until 2013 that Friedl, now at Radboud University in the Netherlands, really felt that he understood what he and his colleagues were seeing. Things finally fell into place for him when he read a paper by Jeffrey Fredberg, a professor of bioengineering and physiology at Harvard University, which proposed that cells could be “jammed” — packed together so tightly that they become a unit, like coffee beans stuck in a hopper.
Fredberg’s research focused on lung cells, but Friedl thought his own migrating cancer cells might also be jammed. “I realized we had exactly the same thing, in 3-D and in motion,” he said. “That got me very excited, because it was an available concept that we could directly put onto our finding.” He soon published one of the first papers applying the concept of jamming to experimental measurements of cancer cells.
Physicists have long provided doctors with tumor-fighting tools such as radiation and proton beams. But only recently has anyone seriously considered the notion that purely physical concepts might help us understand the basic biology of one of the world’s deadliest phenomena. In the past few years, physicists studying metastasis have generated surprisingly precise predictions of cell behavior. Though it’s early days, proponents are optimistic that phase transitions such as jamming will play an increasingly important role in the fight against cancer. “Certainly in the physics community there’s momentum,” Fredberg said. “If the physicists are on board with it, the biologists are going to have to. Cells obey the rules of physics — there’s no choice.”
The Jam Index
In the broadest sense, physical principles have been applied to cancer since long before physics existed as a discipline. The ancient Greek physician Hippocrates gave cancer its name when he referred to it as a “crab,” comparing the shape of a tumor and its surrounding veins to a carapace and legs.
But those solid tumors do not kill more than 8 million people annually. Once tumor cells strike out on their own and metastasize to new sites in the body, drugs and other therapies rarely do more than prolong a patient’s life for a few years.
Biologists often view cancer primarily as a genetic program gone wrong, with mutations and epigenetic changes producing cells that don’t behave the way they should: Genes associated with cell division and growth may be turned up, and genes for programmed cell death may be turned down. To a small but growing number of physicists, however, the shape-shifting and behavior changes in cancer cells evoke not an errant genetic program but a phase transition.
The phase transition — a change in a material’s internal organization between ordered and disordered states — is a bedrock concept in physics. . .