Washington, Aug 16 : Scientists at the University of Texas Medical Branch at Galveston have identified the potential therapeutic target of neuroblastoma, a deadly cancer that primarily strikes infants.
The researchers say that they have basically discovered a critical weakness in cancer that may lead to the development of a lifesaving therapy.
This cancer is generally diagnosed among infants with an average age of 2 years
Lead researcher and Associate professor of surgery Dr. Dai H. Chung showed that shutting down a single biochemical-signalling connection suppresses tumour formation, and slows cancer progression.
The study focussed on an intercellular signalling molecule known as gastrin-releasing peptide (GRP), and the receptor molecule with which it ties up with cell's surface.
GRP activates the production of gastrin, a hormone that among other things controls the release of gastric acid in the stomach; GRP is also produced by neuroblastoma cells and acts to accelerate their proliferation, a discovery made earlier by the UTMB group.
"We had previously demonstrated that GRP stimulates the growth of this particular cancer," said Chung.
"This time we wanted to demonstrate the opposite effects by targeting GRP receptors in neuroblastoma, to see if we could make the cancer regress."
During the study, the researchers took a line of aggressive human neuroblastoma cells and added short-hairpin RNAs, tiny bits of genetic material specifically designed to keep cells from making GRP receptor molecules.
Experiments with the GRP-receptor-silenced human neuroblastoma cells revealed that they grew much less quickly than unaltered neuroblastoma cells, and showed less activity on a biochemical-signalling pathway that is associated with abnormal cell proliferation.
In the study conducted using mouse model, the researchers injected their GRP receptor-silenced neuroblastoma cells into immune-deficient mice.
"We wanted to see how these neuroblastoma cells would behave, whether they would grow and/or metastasize to the liver. But instead, tumour growth was significantly attenuated," said Chung.
In control group mice, by contrast, "the cancer cells that expressed the GRP receptors behaved as we expected with rapid growth as well as aggressive liver metastases. The implication is that the metastatic behaviour of this cancer is driven by GRP and its receptor."