University medical researchers have made a breakthrough in understanding the spread of lung cancer after investigating a substance secreted by cancerous lung cells which stimulates metastasis, or the spread of cancerous tumor cells to other parts of the body.
Researchers initially discovered the cell substance four years ago after finding that when naïve non-lung-cancer cells were exposed to liquid media used to grow metastatic lung cancer cells, the cells displayed metastatic properties.
Marty W. Mayo, one of the researchers on the team and a biochemistry and molecular genetics associate professor, said this led them to believe the metastatic cells were leaving behind proteins which interacted with naïve cells.
“Ultimately we maneuvered the cells in such a way that they showed metastatic properties by using cell culture methods,” Mayo said. “We realized that the cells were able to maintain the metastatic phenotype. Because the factors that we used to make the metastatic cells were already gone, we hypothesized that they must be making their own soluble protein that was stimulating the metastatic process.”
The researchers took a bioinformatics approach to find the solution, a process which needed years of research to navigate the human genome to successfully identify the factor stimulating the metastatic process.
Stefan Bekiranov, biochemistry and molecular genetics associate professor, said he worked on comparing epigenetic factors from cancer cells in the primary tumor and the metastatic phases.
“We mapped 18 epigenetic factors in the meta[static] cells and in the primary tumor cells, and we mapped the levels of genes in the metastatic and the primary tumor cells,” Bekiranov said. “We compared them and we were able to identify genes that were controlled very specifically by the epigenetic factors that were highly associated with the metastatic process.”
By using metastatic and epigenetic data along with a secreted protein database, the researchers were able to narrow the number of potentially causal genes from 20,000 to the one Activin A protein — the protein which appears responsible for the change.
“We showed Activin A was created from cells and we could dump it on cells and it created this metastatic process,” Mayo said. “In cancer cells it’s usually low but when we manipulated them to show the metastatic property, they make a lot of the Activin A.”
Researchers said the next step is to identify a drug which blocks the Activin A protein without blocking other helpful proteins, perhaps by an attempt to block a receptor from inside the relevant cells. Additionally, other genes which appear important to the metastatic process will also be explored as targets.