For breast cancer patients, maintaining adequate oxygen levels may be crucial. In a new study from the University of Johns Hopkins University, researchers show that low oxygen levels increase the production of proteins associated with tumor growth. the discovery may inspire new ways to improve the efficiency of conventional therapy.
Like cancers of the lung, bone, and liver, breast cancer is often exceedingly difficult to treat, as the tumor tends to stray beyond its site of origin. To do this, the cancer must initiate a series of internal changes that facilitate so-called metastasis –– the biological process whereby cancerous cells blight and invade neighboring tissue. The current study, which is published in the journal Proceedings of the National Academy of Sciences, sought to investigate whether any environmental factors can influence the rate of this often fatal process.
According to Gregg Semenza, a professor of medicine and senior author of the study, the results suggests that breast cancer cells are able to take advantage of a biological “emergency measure” aimed at offsetting hypoxia, or lack of oxygen. While helping healthy cells negotiate a less-than-ideal environment, the body inadvertently boost the production of RhoA and ROCK1 proteins associated with breast cancer growth. "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 said, speaking to Medical News Today. “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."
A more detailed lab analysis confirmed this reaction. According to lead author Daniele Gilkes, hypoxia-inducible factors modulate the rate of metastasis by determining the production of so-called “parallel filaments” –– tissue that enables the cancer to “grab” external surfaces and lurch forward. Cancerous cells exposed to low oxygen levels exhibited a three-fold increase in these filaments.
"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 told reporters. “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."
Breast cancer is currently the second most deadly cancer among U.S. women, affecting over 200,000 and killing 40,000 each year. It is estimated that one in every eight women will develop the disease at some point in their life. While the cause remains unknown, risk factors include early puberty, late menopause, and certain genes. Lifestyle factors like calorie intake and alcohol consumption have also been implicated in higher risk for diagnosis.
Source: Daniele M. Gilkes, Lisha Xiang, Sun Joo Lee, Pallavi Chaturvedi, Maimon E. Hubbi, Denis Wirtz, and Gregg L. Semenza Hypoxia-inducible factors mediate coordinated RhoA-ROCK1 expression and signaling in breast cancer cells PNAS 2013 ; published ahead of print December 9, 2013