Unanticipated Discovery: Cellular Division Byproduct Could Play a Role in Cancer Metastasis

The cellular element previously considered to be a waste product, known as the midbody remnant, has been found to contain functional RNA capable of impacting other cells and potentially instigating cancer. This revelation sheds light on its possible involvement in cancer expansion and introduces new possibilities for cancer diagnosis and treatment.

While earlier studies had delved into the midbody’s role in cell signaling and growth stimulation, researchers sought to further explore the internal makeup of these midbody remnants.

Contrary to its previous categorization as a cellular refuse container, the midbody remnant has been found to hold functional genetic material that possesses the ability to alter the destiny of other cells, including transforming them into cancerous cells.

Ahna Skop, a genetics professor at the University of Wisconsin–Madison, states that during cell division, also known as mitosis, the outcome is not simply two daughter cells. “The process results in the formation of three entities: two daughter cells and a separate midbody remnant, which serves as a new signaling organelle,” explains Skop. “What was astonishing to us was the midbody’s storage of genetic information, RNA, which appears to function more in cell communication than in cell division.”

In a recent paper published in the journal I, a collaborative study involving researchers from Skop’s lab, the Pasteur Institute in Paris, Harvard Medical School, Boston University, and the University of Utah, delved into the contents of midbodies that manifest between daughter cells during cellular division. The team traced the interactions of midbody remnants that are released post-division, indicating that the midbody may act as a mechanism for the dissemination of cancer throughout the human body.

“While the midbody was initially thought to be a disposal area post-cell division, it turns out to be a repository of cellular information that cells utilize for communication,” notes Skop.

The internal structure of midbodies revealed RNA—a working replica of DNA used for protein synthesis—as well as the essential cellular machinery for translating that RNA into proteins. Interestingly, the RNA blueprints within midbodies are generally not related to cellular division but rather linked to activities that direct a cell’s function, such as pluripotency and oncogenesis.

“A midbody remnant is remarkably minuscule, with dimensions on the order of a micron, a millionth of a meter,” says Skop. “However, it’s akin to a miniature lunar lander, equipped with everything needed to preserve the functional genetic material originating from the dividing cell. This enables it to drift away from the mitotic site, potentially entering the bloodstream and settling on another cell located at a distance.”

Many midbody remnants are reabsorbed by the daughter cells from which they were released. However, those landing on far-off surfaces might be assimilated by a third cell. This third cell, upon ingesting the midbody, could mistakenly utilize its RNA content as if it were its own.

Future Implications and Research Prospects

Previous studies demonstrated that cancer cells are more likely than stem cells to absorb a midbody and its potentially transformative cargo. Going forward, research may look into leveraging midbody RNA for targeted drug delivery to cancer cells or inhibiting their division.

“We believe that our discoveries could be monumental for the development of new cancer detection methods and therapies,” says Skop, whose research has been financially supported by the National Institutes of Health.

In terms of genetic investigation, the researchers identified a gene named Arc that is crucial for the RNA content of the midbody and its remnant. Originating from an ancient virus, this gene also plays a role in memory formation in brain cells. “The absence of Arc leads to a depletion of RNA in the midbody and hampers the transfer of this RNA information to receiving cells,” states Skop.

The lead author of this groundbreaking study is Sungjin Park, a senior scientist in Skop’s laboratory. Skop and her team also have a patent pending for two novel techniques that facilitate the isolation of midbody structures from cellular media or blood serum, thus enhancing cancer diagnostics.

This research has received partial funding from grants by the National Institutes of Health (R01 GM139695-01A1, R01 NS115716, and R01 GM122893 and GM144352) as well as the French Foundation ARC for cancer research.

Reference: “The mammalian midbody and midbody remnant are assembly sites for RNA and localized translation” by Sungjin Park, Randall Dahn, Elif Kurt, Adrien Presle, Kathryn VanDenHeuvel, Cara Moravec, Ashwini Jambhekar, Olushola Olukoga, Jason Shepherd, Arnaud Echard, Michael Blower and Ahna R. Skop, published on August 7, 2023, in Developmental Cell.
DOI: 10.1016/j.devcel.2023.07.009

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More about midbody remnants

• Original Research Article in Developmental Cell
• University of Wisconsin–Madison Genetics Department
• National Institutes of Health Funding
• French Foundation ARC for Cancer Research
• Pasteur Institute in Paris
• Harvard Medical School
• Boston University
• University of Utah
• Overview of Cellular Division
• Introduction to RNA