Low oxygen conditions, which often persist inside tumours, are sufficient to initiate a molecular chain of events that transforms breast cancer cells from being rigid and stationery to mobile and invasive, finds scientists.
Gregg Semenza, M.D., Ph.D., the C. Michael Armstrong Professor of Medicine at the Johns Hopkins University School of Medicine, said that high levels of RhoA and ROCK1 were known to worsen outcomes for breast cancer patients by endowing cancer cells with the ability to move, but the trigger for their production was a mystery.
He said that they now know that the production of these proteins increases dramatically when breast cancer cells are exposed to low oxygen conditions.
To move, cancer cells must make many changes to their internal structures, Semenza said.
Thin, parallel filaments form throughout the cells, allowing them to contract and cellular "hands" arise, allowing cells to "grab" external surfaces to pull themselves along. The proteins RhoA and ROCK1 are known to be central to the formation of these structures.
Moreover, the genes that code for RhoA and ROCK1 were known to be turned on at high levels in human cells from metastatic breast cancers.
In a few cases, those increased levels could be traced back to a genetic error in a protein that controls them, but not in most. This activity, said Semenza, led him and his team to search for another cause for their high levels.
The researchers found that women with high levels of RhoA or ROCK1, and especially those women with high levels of both, were much more likely to die of breast cancer than those with low levels.
The study is published in Proceedings of the National Academy of Sciences.