The scientists then examined microRNA production in five additional commonly studied human and mouse cell lines, including human breast cancer cells, human colorectal cancer cells and human pancreatic cancer cells. They also tested fruit fly cells to determine whether or not the phenomenon is restricted to mammals.
In all tested cell lines, including the fruit fly cells, scientists observed a dramatic increase in microRNA abundance with increasing cell density.
"All evidence points to the fact that physical contact -- when cells actually touch each other -- is the critical factor that revs up the production of microRNAs," Mendell says. "Through additional experiments, we were able to identify the specific molecular steps at which microRNA production is affected. We expect that this phenomenon will profoundly influence how cells behave in normal development and disease."
The team's finding has practical importance for researchers who are investigating a range of biological processes that are most conveniently studied in cells growing in culture, Mendell says: "Little did we know the manufacture of microRNAs was so potently influenced simply by growing cells to different densities. We now recognize that this is a critical parameter that must be closely monitored when performing experiments with microRNAs in tissue culture."
A better understanding of how microRNA production is regulated is important because a reduction in the abundance of these molecules has been linked to the development of certain cancers. To date, one barrier to understanding how microRNAs are regulated in normal development and in disease states has been the lack of a simple system by which scientists could turn on and off a molecular pathway that controls microRNA production. Now, it seems, they may be able to toggle that pathway using cell-to-cell contact.
"If we can identify the mechanisms throu
|Contact: Maryalice Yakutchik|
Johns Hopkins Medical Institutions