A new way to target tumors
Study shows how one enzyme helps tumor cells thrive
By Czerne M. Reid
Whether a tumor flourishes or dies depends, to an extent, on the acidity of the environment in which it lives, and a certain enzyme plays a key role in that balance, according to new UF research.
An enzyme known as carbonic anhydrase IX influences tumor biology by working to keep acidity — or pH — at a level at which normal cells perish, but cancer cells thrive.
“We don’t know why cancer cells can tolerate low pH — but they do, and we believe that carbonic anhydrase is a significant player in picking the specific pH at which the cells are happiest,” said biochemist Susan Frost, Ph.D., of the UF Shands Cancer Center, who led the research team.
The enzyme may serve as a new and important target for visualizing, diagnosing and treating cancer. The findings are published in the Journal of Biological Chemistry.
Breast cancers are often characterized by oxygen-deprived regions that clinicians generally use as an indicator of poor prognosis in patients. Such oxygen-deprived — or hypoxic — regions occur when new blood vessels that form to feed a tumor become compressed, cutting off circulation and the supply of oxygen and nutrients. Lack of oxygen leads to metabolic processes that make the cells’ external environment more acidic. Those conditions favor cancer cell survival and resistance to chemotherapy agents.
The enzyme carbonic anhydrase IX is expressed in connection with these oxygen-deprived areas.
The researchers were able to show, for the first time, a direct link between an increase in both the production and the activity of the enzyme and oxygen deprivation in tumor cell environments. Further, the UF scientists showed directly that the lowering of pH occurred as the activity of the enzyme increased.