Giant cancer cell properties probed for potential treatment targets
As if cancer wasn't scary enough already, it turns out the cells have video game-style boss versions that are bigger, more resilient and can travel further. These so-called "giant" cancer cells contribute to many of the disease's most dangerous abilities, but they remain relatively unstudied. Now, researchers from Brown University have investigated these troublemakers, revealing some physical characteristics that could eventually unlock new forms of treatment.
These giants – more technically known as polyploidal cancer cells – are much larger than regular cancer cells because they contain more than the usual two copies of each chromosome. These cells are harder to kill using chemotherapy and radiation, and while they may go into hiding following these treatments, they're often the first ones to come back and trigger a relapse later on.
"I think these polyploidal giant cancer cells are the missing link for why tumors become so complex and heterogeneous so quickly," says Michelle Dawson, corresponding author of the study. "By understanding the physical properties of this weird population of cells we might identify a new way to eliminate them. Patients will benefit from that."
To investigate, the Brown researchers studied the common and extremely aggressive triple negative breast cancer. The team found that between two and five percent of the cancer cells were polyploidal, containing either four, eight or 16 copies of each chromosome. As expected, those cells were much larger than their regular counterparts.
The researchers then treated the breast cancer cells with chemotherapy, and checked their polyploidal cell levels. Afterwards there were three to 10 times more giant cells than there were originally, indicating that these cells were indeed more drug resistant.
Next, the researchers measured some of the giant cancer cells' other properties. They found that injected fluorescent nano-beads moved through these cells at only about half the speed that they would through normal cancer cells. That means they're stiffer, which contributes to their larger size. The giant cells also had more actin, a structural protein that gives them their shape and mobility, which allows them to travel further – albeit more slowly – through the body, aiding metastasis.
"The giant cancer cells break all the cancer rules – they are stiffer, they are larger, they have a very abnormal and non-polarized cell structure – and they can move a long way," says Dawson. "Without basic science research, we don't get creative new ideas that lead to breakthrough treatments for patients."
One such idea that the team tested was a drug that interferes with actin. While the researchers did find that it softened up the polyploidal cells, it's not a viable treatment in its current form, since it would also attack healthy cells the same way. Still, it opens up new potential pathways for future treatments, and the researchers say that the next step could be to look for molecular differences that could help with development of a more targeted treatment.
The research was published in the journal Scientific Reports.
Source: Brown University