Cancer Cells Appropriate Signaling Pathway Used by Neurons to Metastasize

Scientists have discovered that breast and lung tumors can appropriate a signaling pathway used by neurons to metastasize. In a study published today in Nature, researchers describe how these cancer cells enlist nearby blood vessels to gain access to this nerve signal, ultimately enabling their escape from the primary tumor and into the bloodstream.

"We hypothesized that cells in the inner lining of blood-vessels send a signal that instructs cancer cells within the primary tumor to metastasize," said lead researcher Sohail Tavazoie. The team set out to look for that signal using a modified form of TRAP, a technology that makes it possible to pinpoint subtle differences between otherwise similar cells and the proteins they produce. Ultimately, they identified the signal as Slit2, a protein normally produced by neurons. In addition, they were able to explain how cancer cells get their hands on it.

This signaling molecule is known to help guide nerve-cell extensions as they travel from one part of the brain to the other. The researchers found that breast and lung cancer cells use an intricate mechanism to coax blood-vessel cells into making and releasing Slit2—just enough of a dose to help the cancer cells start migrating. 

"The cells first activate normally silenced DNA to produce double-stranded RNA, which in turn acts as a signal to trigger their own movement out of the primary tumor and into the blood, from where they can spread to other organs," he says. "There's also a chance that inhibiting these pathways could open the door to novel cancer drugs that curb metastasis.”