The growth of tumors depends in part on its microenvironment, a dynamic area surrounding the tumor, which can include normal cells, supporting structures and molecules. Cancer cells can exert a major influence on the tissue around them, reshaping and remodeling it to meet the demands of the tumor. Scientists have been learning more about tiny sacs called microvesicles that are released by tumors cells into the microenviroment. The extracellular microvesicles contain molecules from inside the tumor cell, including microRNA that triggers protein production. Those microvesicles can also move into circulation.
New research has found that extracellular microvesicles can also carry DNA from the tumor to other cells, promoting the spread or metastasis of cancer. Cancer is most deadly when it's metastatic. The findings have been outlined in Cell Reports.
"We've shown that DNA present in these microvesicles is related to metastasis, so now we have a great platform to assess for genetic aberrations," said senior study author Professor Crislyn D'Souza-Schorey of the University of Notre Dame.
In normal cells, DNA is typically contained in the nucleus. But in cancer cells, the cytosol is often filled with DNA. That so-called cytosolic DNA seems to come primarily from unstable chromosomes.
In this study, the researchers generated cells from the sample of a volunteer, a male cancer patient. The scientists showed that DNA from unstable Y chromosomes in those cancer cells made its way into the cytosol, and was able to migrate into different cells, which were from the female mammary epithelium.
Since female cells don't carry Y chromosomes, they could only have obtained that DNA from the male cancer cell microvesicles. "This is an accessible way to show people that the DNA was transferred, making it easier to prove this form of communication," explained first study author James Clancy, a research assistant professor of biological sciences.
An enzyme called cGAS was found helping move the cytosolic DNA into microvesicles. Previous research has indicated that cGAS could be involved in the progression of tumors, which this study seems to confirm.
The microvesicles released by tumor cells can be used as biomarkers. This study has shown that the molecules in those microvesicles can move from one cell into another. DNA in tumors is often highly mutated, which could make those microvesicles very dangerous for the rest of the body, but may also help create better diagnostic tools or therapuetic insights.