Tumour "Tweets" Influence Other Cells

Groundbreaking research from Australia reveals that brain tumours release small bits of information, rather like "tweets", that interact with blood vessel cells in a way that causes them to undergo significant changes. The researchers believe the discovery may lead to new treatments.

Writing in the 17 June online issue of RNA Biology, Michael Buckland, associate professor in the University of Sydney's Brain and Mind Research Institute (BMRI), and colleagues, describe how they found brain tumours release microvesicles containing new forms of RNA, and these interact with nearby brain blood vessel cells. Microvesicles Are Like "Tweets" RNA (short for ribonucleic acid), a close cousin of DNA, is a group of long-chained molecules that among other things, control gene expression and help transfer the genetic code held in DNA to make proteins. Microvesicles are tiny pockets of cell plasma, enclosed in a membrane.

They are released by cells and were once considered to be junk, or debris. Buckland says scientists are just becoming aware of the significance of microvesicles, and how they may be important for health and disease. For instance, there have been suggestions that microvesicles may have potential as clinical biomarkers for individual cancers. "It seems that many cells release microvesicles allowing them to communicate and influence other cells nearby and in distant parts of the body in real-time - much like tweeting," Buckland says in a statement. Modification of the Environment Is Important for Tumour Growth Tumours thrive in different environments to healthy tissue. As the tumour grows it interacts with its environment, for instance changing the blood supply to suit its own needs. To do this the tumour must interact with other cells, and modify their gene expression so they make the proteins that suit the tumour rather than those that suit healthy tissue. The team had a hunch that one way brain tumour cells (gliomas) do this is via the microvesicles. So they designed a study that took an "unbiased approach to identifying RNAs in glioma-derived microvesicles, and explored their potential to regulate gene expression in recipient cells".

Microvesicles from Brain Tumour Cells Contained More Unusual RNA For the study, the team grew brain tumour cells (gliomas) in culture and harvested the microvesicles they released into the culture medium. When they added the glioma-produced microvesicles to cultures of brain blood vessel cells, they triggered significant changes in the cells, including many changes in gene expression. On closer examination they found that the glioma microvesicles contained complex populations of coding and non-coding RNA, and the proportions of these populations were different to those from the cells they came from. Compared to the glioma cells that made them, glioma microvesicles had lower levels of microRNA and higher levels of unusual or new non-coding RNA, most of which "have no known function", write the authors, who conclude: "Our data suggest that the scope of potential actions of tumor-derived microvesicles is much broader and more complex than previously supposed, and highlight a number of new classes of small RNA that remain to be characterized."

Microvesicles Could Be Target for New Treatments and Aids for Diagnosis. Buckland says their findings suggest microvesicles "likely to play an important role in the changes to blood vessels seen in high grade brain tumours, the most common form in Australian adults". They present a new target for treatment against brain tumours, he says, adding that: "Furthermore, they can be detected in the blood of patients with brain tumours, and may be an important diagnostic tool in the future." A biosciences company has also suggested, at a scientific meeting in 2011, that the fact circulating microvesicles have different RNA profiles highlights their potential use in cancer detection and monitoring.