Diagnosing Cancer With Help From Bacteria

Diagnosing Cancer With Help From Bacteria
(Illustration: Christine Daniloff/MIT)
Many types of cancer, including colon and pancreatic, tend to metastasize to the liver. The earlier doctors can find these tumors, the more likely that they can successfully treat them. Engineers have devised a new way to detect cancer that has spread to the liver, by enlisting help from probiotics - beneficial bacteria similar to those found in yogurt.
Using a harmless strain of E. coli that colonizes the liver, the researchers programmed the bacteria to produce a luminescent signal that can be detected with a simple urine test. The research is published in the journal Science Translational Medicine.
Previous studies have shown that bacteria can penetrate and grow in the tumor microenvironment, where there are lots of nutrients and the body's immune system is compromised. Because of this, scientists have been trying for many years to develop bacteria as a possible vehicle for cancer treatment, as well as creating a bacterial diagnostic.
To turn bacteria into diagnostic devices, the researchers engineered the cells to express the gene for a naturally occurring enzyme called lacZ that cleaves lactose into glucose and galactose. In this case, lacZ acts on a molecule injected into the mice, consisting of galactose linked to luciferin, a luminescent protein naturally produced by fireflies. Luciferin is cleaved from galactose and excreted in the urine, where it can easily be detected using a common laboratory test.
At first, the researchers were interested in developing these bacteria for injection into patients, but then decided to investigate the possibility of delivering the bacteria orally, just like the probiotic bacteria found in yogurt. To achieve that, they integrated their diagnostic circuits into a harmless strain of E. coli called Nissle 1917, which is marketed as a promoter of gastrointestinal health.
In tests with mice, the researchers found that orally delivered bacteria do not accumulate in tumors all over the body, but they do predictably zero in on liver tumors because the hepatic portal vein carries them from the digestive tract to the liver.
This allowed the team to develop a diagnostic specialized for liver tumors. In tests in mice with colon cancer that has spread to the liver, the probiotic bacteria colonized nearly 90 percent of the metastatic tumors.
In the mouse experiments, animals that were given the engineered bacteria did not exhibit any harmful side effects.
The researchers focused on the liver not only because it is a natural target for these bacteria, but also because the liver is hard to image with conventional imaging techniques like CT scanning or magnetic resonance imaging (MRI), making it difficult to diagnose metastatic tumors there.
With the new system, the researchers can detect liver tumors larger than about one cubic millimeter, offering more sensitivity than existing imaging methods. This kind of diagnostic could be most useful for monitoring patients after they have had a colon tumor removed because they are at risk for recurrence in the liver.
Based on material originally posted by Massachusetts Institute of Technology.