Cell Rep: Discovery of a new pathway for DNA transfer in the tumor microenvironment

In their latest study, published in Cell Reports, Crislyn D'Souza-Schorey, the Maurice Pollard Professor in the Department of Biological Sciences, and collaborators found that DNA "cargoes" are transported in microvesicles called extracellular microvesicles.

"We've shown that DNA is present in these microvesicles with transference, and now we have an excellent platform to assess genetic aberrations," said D'Souza-Schorey, who is also affiliated with the Berthiaume Institute for Precision Health, Boler-Parseghian Center for Rare and Neglected Diseases and Harper Cancer Institute

Unlike normal cells, cancer cells are usually full of cytoplasmic DNA, the DNA found in the jelly-like fluid outside the nucleus

The research team used a cell model of a male cancer patient to show how y-chromosome DNA -- present in the cytoplasm due to chromosomal instability -- is carried by extracellular vesicles and transferred to a female breast epithelial cell line

"Without exposure to male microvesicles, the y-chromosomal DNA would not be present in these female cells," said James Clancy, assistant professor of biological sciences and lead author of the paper

The researchers demonstrated that cytoplasmic DNA is transferred into microvesicles along with an enzyme called cGAS, which was discovered in part for its role in the immune response to bacterial and viral infections

Research published in Nature Cell Biology in 2019 by D'Souza-Schorey's lab describes how microRNAs within tumor cells are transferred to microvesicles that are just beginning to form at the cell periphery

While microRNAs can affect protein expression more quickly than DNA, researchers are interested in the amount of DNA because it's the actual part of a person's genome, including any tumor-associated mutations, Clancy said

The laboratory's continued basic research in this area may lead to early detection of different types of tumors

In addition to D'Souza-Schorey and Clancy, others involved in the study include Colin Sheehan, Class of 19, and Alex C.

Journal Reference :

1. James W.