Once thought to be cellular waste, midbody residues contain functional RNA that can affect other cells and even cause cancer. The discovery highlights its potential role in cancer proliferation and provides new avenues for cancer detection and treatment.
The role of midbodies in cell signaling and stimulating cell proliferation has been studied before, but the researchers wanted to delve deeper inside the midbody remnants to learn more.
Once thought of as the cell's trash can, a small bubble of cellular material called a midbody remnant is actually packaging working genetic material with the ability to alter the fate of other cells, including turning them into cancer.
Ahna Skop, a professor of genetics at the University of Wisconsin-Madison, said that what surprises many people is that when a cell divides in two (a process called mitosis), the result is more than just two daughter cells.
"A cell divides into three parts: two cells and a midbody remnant, a new signaling organelle," Schop said. "To our surprise, the intermediate was filled with genetic information, RNA, which doesn't have much to do with cell division but may play a role in cell communication."
Bright green-labeled RNA translation reveals that two human cells about to separate are still connected by red microtubules, which provide some structure during cell division. The green dot in the middle is the intermediate, a structure that will be released when division is complete and free to carry its important genetic material to other cells. Image source: Scoop Laboratory, University of Wisconsin-Madison
In a recent study published in the journal I, Schop's lab and collaborators at the Institut Pasteur in Paris, Harvard Medical School, Boston University, and the University of Utah analyzed the contents of midsomes—those formed between daughter cells during division—and tracked the interactions of midbody remnants released after cell division. Their findings suggest that mesosomes serve as vectors for cancer to spread throughout the body.
"The midbody is thought to be where cells die or are recycled after dividing," Schop said. "But one person's trash is another person's treasure. Intermediates are little packets of information that cells use to communicate."
The involvement of midbodies in cell signaling and stimulating cell proliferation has been studied before, but Scope and her collaborators wanted to delve deeper into the interior of midbody remnants to learn more.
In the intermediate, the researchers discovered RNA (a working copy of DNA used to make proteins that make things happen in cells) and the cellular machinery necessary to convert RNA into proteins. The RNA in the intermediates tends not to be a blueprint for the process of cell division, but for proteins involved in activities that direct the cell's uses, including pluripotency (the ability to develop into many different types of cells in the body) and tumorigenesis (the formation of cancerous tumors).
"The mesobody remnant is very small. It's a micron in size, a millionth of a meter," Scope said. "But it's like a small moon lander. It has everything it needs to maintain the working information of a dividing cell. It can travel away from the site of mitosis, enter your bloodstream and land on another cell far away."
Many midbody remnants will be reabsorbed by one of the shed daughter cells, but those that land on a distant surface (such as a lunar lander) may be absorbed by a third cell. If the cell engulfs the midbody, it may mistakenly start using the blocked RNA as if it were its own blueprint.
Previous research has shown that cancer cells are more likely than stem cells to take in intermediates and their potentially fate-altering substances. Stem cells, capable of generating new cells and valuable for their pluripotency, spit out large amounts of intermediates, perhaps to maintain their pluripotency.
Future research may be able to harness the power of midbody RNA to deliver drugs to cancer cells or prevent them from dividing.
"We believe our findings represent a huge target for cancer detection and treatment," said Schop, whose work is supported by the National Institutes of Health.
The researchers discovered a gene called Arc that is critical for loading RNA into the midbody and midbody remnants. Arc was extracted from an ancient virus long ago, and it also plays an important role in the process by which brain cells form memories.
"Loss of Arc results in loss of RNA in the midbody and loss of the RNA message reaching the recipient cell," Skop said. "We believe this memory gene is important for all cells to transmit RNA messages."
Sungjin Park, a senior scientist at Scoop Labs, is the lead author of the new study. Scope and collaborators are also patenting two new methods that could improve cancer diagnostics by making it easier to isolate intermediate structures from cell media or serum.