New research suggests the low-oxygen conditions inside a tumor can be what triggers cells to go from "rigid and stationery to mobile and invasive."
The researchers suggest hypoxia-inducible factors could help patients avoid metastasis, a Johns Hopkins Medicine news release reported.
"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," says Gregg Semenza, M.D., Ph.D., the C. Michael Armstrong Professor of Medicine at the Johns Hopkins University School of Medicine and senior author of the article. "We now know that the production of these proteins increases dramatically when breast cancer cells are exposed to low oxygen conditions."
In order to move malignant cells must modify their internal structures. The cells develop parallel filaments that act as "hands" to grab onto surfaces and pull them along. These hands are believed to be "the central formation of these features, the news release reported.
The team believes low-oxygen conditions inside a tumor could trigger this formation.
"As tumor cells multiply, the interior of the tumor begins to run out of oxygen because it isn't being fed by blood vessels," Semenza asid. "The lack of oxygen activates the hypoxia-inducible factors, which are master control proteins that switch on many genes that help cells adapt to the scarcity of oxygen."
Daniele Gilkes, Ph.D., a postdoctoral fellow and lead author of the report looked at cells in lab-made low oxygen conditions, and found they were much more mobile than they would be in a more "breathable" environment. The cells in low oxygen conditions had three times the amount of filaments as those in lower level environments.
The team also found a big increase in the RhoA and ROCK1 proteins in low-oxygen conditions; but observed a decrease when the number of hypoxia-inducible factors was reduced.
The researchers found women with higher levels of RhoA or ROCK1 were more likely to die from breast cancer.
"We have successfully decreased the mobility of breast cancer cells in the lab by using genetic tricks to knock the hypoxia-inducible factors down," Gilkes said. "Now that we understand the mechanism at play, we hope that clinical trials will be performed to test whether drugs that inhibit hypoxia-inducible factors will have the double effect of blocking production of RhoA and ROCK1 and preventing metastases in women with breast cancer."
