Discovery of a new pathway allowing tumor cells to transfer genetic material

Researchers at the University of Notre Dame have discovered another way tumor cells transfer genetic material to other cells in their microenvironment, causing cancer to spread.

In their latest study, published in Cell Reports, Crislyn D’Souza-Schorey, Professor Morris Pollard in the Department of Biological Sciences, and her collaborators found that DNA “cargo” is carried in small bags of information called microvesicles. extracellular. Their study is a continuation of the work that his laboratory has undertaken to better understand the sharing of information between cells.

“We have shown that the DNA present in these microvesicles is linked to metastasis, so we now have an excellent platform to assess genetic aberrations,” said D’Souza-Schorey, who is also affiliated with the Berthiaume Institute for Precision Health, the Boler-Parseghian Center for Rare and Neglected Diseases, and the Harper Cancer Research Institute.

Cancer cells, unlike normal cells, are often filled with cytosolic DNA, which is DNA found in the gelatinous fluid outside the cell’s nucleus. This DNA can come from several sources, but recent evidence suggests that chromosomal instability is a primary source of cytosolic DNA in tumor cells.

The research team used a cellular model of a human with cancer to show how DNA from the Y chromosome – present in the cytosol due to chromosomal instability – is transported by extracellular vesicles and transferred to a female mammary epithelial cell line.

“These female cells do not have Y-chromosomal DNA present without exposure to male microvesicles,” said James Clancy, assistant research professor of biological sciences, who is the paper’s first author. “It’s an accessible way to show people that DNA has been transferred, making it easier to prove this form of communication.”

The researchers demonstrated that cytosolic DNA is moved into microvesicles alongside an enzyme, cGAS, which was discovered in part because of its role in the immune response to bacterial and viral infections. Scientists are increasingly recognizing that cGAS may play a role in tumor progression, and this new study has described a way in which DNA is modified to facilitate this progression.

Work published by D’Souza-Schorey’s lab in 2019 in Nature Cell Biology described how microRNA in tumor cells is moved to microvesicles that are just beginning to form at the cell periphery. Once excreted, these vesicles are taken up by non-tumor cells in the microenvironment. Microvesicles can also circulate in the body in fluids such as blood and urine, and can be used as biomarkers indicating the presence of cancer.

While microRNAs can affect protein expression faster than DNA, researchers were interested in DNA content because it is the actual part of a person’s genome, including tumor-associated mutations. , Clancy said. It was also more difficult to prove that DNA had moved from cell to cell.

Further fundamental laboratory research in this area could lead to the early detection of different types of tumours.

Reference: Clancy JW, Sheehan CS, Boomgarden AC, D’Souza-Schorey C. DNA recruitment in tumor-derived microvesicles. Cell reports. 2022;38(9). doi: 10.1016/j.celrep.2022.110443.

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