"The aggressive breast cancer cells grow rapidly and normally appear spindle-shaped or thin and elongated. Remarkably, within a few days of blocking HMGA1 expression, they appeared rounder and much more like normal breast cells growing in culture," says Resar. The team also found that the cells with suppressed HMGA1 grow very slowly and fail to migrate or invade new territory like their HMGA1-expressing cousins.
The team next implanted tumor cells into mice to see how the cells would behave. The tumors with HMGA1 grew and spread to other areas, such as the lungs, while those with blocked HMGA1 did not grow well in the breast tissue or spread to distant sites.
"From previous work, we know that HMGA1 turns on many different genes needed during very early development, but it's normally turned off by the time we're born," says postdoctoral fellow Sandeep Shah, Ph.D., who led the study. "Flipping that master regulator back on seems to be necessary for a cancer to become highly aggressive, and now we've seen that flipping HMGA1 off again can reverse that aggressive behavior."
The next step, Resar says, is to try to develop a therapy based on that principle. The team is working with other researchers at Johns Hopkins to see whether HMGA1-blocking molecules could be delivered to tumors inside nanoparticles. Another possible approach, she says, would be to block not HMGA1 itself, but one of the pathways or processes that it affects.
|Contact: Shawna Williams|
Johns Hopkins Medicine