The fragments travel along wispy threads connecting cells
Damaged DNA can escape from one human cell and enter another.
Like prisoners leaving prison, this DNA travels via tubular structures between neighboring cellsscientists report on May 19 in Cell. Once it arrives at its new location, the questionable DNA can begin to react, potentially transferring problems between cells.
“This is an important and exciting finding,” says Stanford University cancer biologist Paul Mischel. The new study, which shows that one human cell can influence another by directly passing DNA, raises all sorts of questions about the role this phenomenon may play in cancer.
If tumors use this DNA transfer trick, harmful mutations could potentially spread from cancer cells to healthy cells, says Peter Ly, a cancer cell biologist at the Children’s Medical Center Research Institute at UT Southwestern in Dallas. How — or if — these stray DNA fragments might contribute to disease is “an area we’re actively exploring,” Ly says.
His team first observed traveling DNA after mixing two types of cells in the laboratory. When the researchers triggered damage to the genome, a cell’s complete set of genetic instructions, they noticed that fragments of DNA appeared to move between cells.
Human DNA generally remains protected in the nucleus and does not move from cell to cell. Looking through a microscope, Ly’s team saw living cells connected by wispy threads, like strands of spun sugar. Scientists have known about these threads, called tunneling nanotubes, for decades. They are like highways for transporting goods between cells. Cancer cells can use nanotubes to steal mitochondria, the cell’s energy plants, from their neighbors, and even send their own mitochondria to “brainwash” healthy cells.
But until now, no one had seen DNA traveling along these intercellular highways. And Ly’s team discovered that the traveling DNA wasn’t just a useless genomic jet. This could provide functional characteristics. In one experiment, researchers showed that an antibiotic resistance gene introduced into the Y chromosome of male cells could be transferred to neighboring female cells.
Key to launching the journey was the introduction of errors or damage into the genome – a common hallmark of cancer. Inside a tumor cell, chromosomes may be rearranged and genes may be misduplicated or contain other mutations. It’s possible that such errors cause tumor cells to send criminal genomic fragments to surrounding cells, says physician-scientist Christoph Gerdes, who does cancer research at the Princess Margaret Cancer Center in Toronto. This could be problematic for several reasons. Fragments that allow cancer to resist chemotherapy, for example, could spread between cells, making the disease more difficult to treat. It’s too early to tell if that will happen, Gerdes says, but Ly’s work “opens up new possibilities.”
Previous research suggested that human cells might exchange DNA via tiny bubbles that pass between cells. And the work of Gerdes and geneticist Buket Basmanav suggests that DNA fragments could be transferred somehow if the cells were in close contact. Ly’s team’s new work puts “a few pieces of the puzzle together” in an elegant and compelling way, says Basmanav, of the University of Bonn in Germany. This provides strong evidence that DNA transfer occurs via nanotubes, she says.
Ly and his colleagues have a long list of questions they now seek to answer. How often does this type of DNA transfer occur? Can researchers detect transfer events in different tumor types? Do DNA fragments hitch a ride along established cargo routes between cells or trigger the formation of new ones? “We still have a lot of work to do to understand all of this,” says Ly.