Select Amino Acids Play Critical Role in Cancer Blood Supply

Several amino acids known as RNA synthetases were recently found to have an unexpected additional role in cancer metastasis, according to a study conducted collaboratively in the labs of Karen Lounsbury, Ph.D., University of Vermont professor of pharmacology, and Christopher Francklyn, Ph.D., UVM professor of biochemistry.

The group determined that threonyl tRNA synthetase (TARS) leads a "double life," functioning as a critical factor regulating a pathway used by invasive cancers to induce angiogenesis - the formation of new blood vessels - and a new food supply to sustain their growth.

The teams' research was published online February 21, 2013 in Nature Scientific Reports.

According to Tamara Williams, Ph.D., first author on the study and a lecturer in nursing and postdoctoral fellow in pharmacology at UVM, cancerous tumors quickly outgrow their local blood supply. When they do, the cancer cells send out signals, TARS is secreted, and the angiogenesis process is initiated.

"In our study, we showed that TARS, once thought to only function in the housekeeping role of protein synthesis within cells, 'moonlights' as a secreted signaling agent in the endothelial cells that line vessels, in response to factors commonly produced by cancer cells," says Williams.

The study's in vivo model of angiogensis was performed using a chick chrioallantoic membrane assay, according to the University of Vermont. This experiment utilizes the vascular membrane that surrounds a 10-day-old chicken embryo that was removed from its shell. Researchers placed small pieces of surgical sponges on the surface of the membrane and added compounds, including TARS, to the sponges,which were then captured through image every 24 hours.

Their test determined whether the compound was angiogenic (creates new blood vessels), had no effect, or was angiostatic (inhibits blood vessel development). Using this assay, the group was able to demonstrate that TARS prompts angiogenesis by increasing the directional movement, or migration, of vessel cells towards the cancer cell signals. The group's research also showed that a potent inhibitor of TARS activity - called inhibitor BC194 - blocked its induction of angiogenesis.