The findings, published in the January 5 issue of the journal Nature, provide important new insights into the biology of metastatic disease and lay the necessary groundwork for developing targeted therapies designed to halt the spread of neuroblastoma, and possibly other cancers.
"A major problem with cancer is not necessarily the primary tumor formation, but the ability of some tumor cells within that primary tumor to metastasize, or travel to distant sites, where they develop new tumors," said David Cheresh, Ph.D., senior author on the paper and Associate Director for Translational Research at the Moores UCSD Cancer Center. Cheresh is also a professor of pathology at the UCSD School of Medicine.
Caspase 8's normal role is to act as a suicide gene, killing the cell it is housed within in response to cues from the immune system. The UCSD group had previously shown, in normal human cells, that caspase 8 can be activated even without signals from the immune system, particularly when the cell is present in a foreign location. This acts as a mechanism to ensure the cells would survive only in appropriate tissues; for example, liver cells in liver tissue and skin cells in skin tissue.
"The exciting point of the new research is that we are finding that even tumor cells will try to make sense of their location, and when they cannot, they will often activate this suicide pathway," said Dwayne Stupack, Ph.D., first author on the paper and assistant professor of pathology at UCSD.