Researchers at Virginia Tech have identified new ways that cancer cells with abnormal chromosome counts drive tumor growth, according to Science Daily. Their work shows that these cells can pull in healthy connective tissue to support tumors, and that the smaller among them tend to produce more aggressive disease.
The findings were published in the Proceedings of the National Academy of Sciences, with related results appearing earlier this year in Cancer Research, Science Daily reports.
Why it matters
Not all cancers behave the same way. Some expand quickly, invade surrounding tissue, and resist the drugs used against them, while others are far more manageable. Understanding what separates the two could help explain why some patients fare worse than others.
The Virginia Tech work points to a specific type of abnormal cell as part of the answer. It also raises the possibility that something as simple as cell size could one day help signal how dangerous a tumor is likely to be.
Abnormal chromosome counts and the rise of tetraploid cells
Most cells in the human body carry two full sets of chromosomes, one from each parent. When those cells divide, they normally pass the same arrangement on to their offspring. Errors sometimes occur, leaving a cell with the wrong number of chromosomes, and if those errors carry through later divisions, they can build up over time. Science Daily reports that this accumulation is one route by which cancer can develop.
For roughly five years, graduate students Megan Sweet and Mat Bloomfield have studied these abnormal cells alongside cell biologist Daniela Cimini. Their focus is a variant called a tetraploid cell, which holds four complete chromosome sets instead of the usual two.
The team created these cells in the lab by manipulating ordinary cancer cells so they copied their chromosomes without finishing division. Tetraploid cells are not just a laboratory artifact, according to Science Daily. They also appear as human tumors develop, and their presence has been tied to cancer progression and worse patient outcomes.
Scientists already knew that tetraploid cells can make tumors more aggressive. What was missing was an explanation of how they do it.
How a small fraction of abnormal cells reshapes a tumor
To find out, Sweet and Bloomfield set up a comparison. They tracked tumors that grew from standard cancer cells against tumors that grew from tetraploid cancer cells, using mice as the host.
Something unexpected showed up in the data. As the tumors expanded, the share of tetraploid cells inside them fell. Even so, the tumors kept growing fast and reached large sizes.
The explanation, the researchers found, lay outside the cancer cells themselves. Tetraploid cells were drawing in stromal cells, which are noncancerous connective tissue cells that give tumors structural support. Those recruited cells appeared to build conditions that helped the tumor keep developing.
Sweet said that even a small percentage of these tetraploid cells is enough to bring in extra noncancerous cells that support further tumor progression, Science Daily reports. The result describes a mechanism that had not been recognized before: abnormal cancer cells can push a tumor forward while making up only a minor part of its bulk.
Smaller tetraploid cells prove more aggressive
A second line of inquiry produced another surprise. Bloomfield was studying the physical traits of tetraploid cells when he grew them from human cancer cells and established colonies descended from single cells. The colonies were not uniform in size.
Since tetraploid cells carry double the usual number of chromosome sets, the team expected them to be about twice as large as ordinary cells. Instead, the smaller colonies turned out to be the more dangerous ones.
Bloomfield said the smaller clones are more aggressive, growing faster, invading more readily, and withstanding common anti-cancer and stress-inducing drugs better than the larger ones, according to Science Daily.
Experiments in mice backed up what the team had seen in the lab. Tumors made up of smaller tetraploid cells often grew faster than those containing larger ones. The pattern held across more than one cancer type, with similar results in colorectal and breast cancer cells. That suggests the link between tetraploid cell size and tumor aggressiveness may apply across different cancers.
Painstaking lab work behind the results
The conclusions rest on years of slow, exacting bench work. Sweet spends much of her time preparing tumor slices thin enough for light to pass through them. Working in a refrigerated metal chamber, she positions a tumor about the size of a pinkie fingernail against a sharp blade.
Sweet described the process as a matter of fine-tuning to get an even slice, and called it the hardest and most time-consuming part of the work, though also somewhat meditative, Science Daily reports. Each cut section is transferred to a glass slide, where selected structures are stained so they stand out under a powerful microscope. Cutting, staining, examining, and comparing repeat over and over.
That repetition is what allowed the team to compare tumors cell by cell and spot patterns that would otherwise stay hidden.
The research adds detail to a long-standing observation about tetraploid cells and poor outcomes, and it opens two practical questions. One is whether the presence of stromal cells recruited by tetraploid cancer cells could be disrupted as a treatment strategy. The other is whether measuring the size of tetraploid cells in a patient's tumor could help predict how aggressively that cancer will behave.
Both ideas remain untested in people. For now, the work stands as an explanation of mechanism rather than a new therapy, and further studies will be needed to see whether either finding changes how cancers are assessed or treated.
