Targeting metastasis to halt cancer’s spread

Abstract

Studies reveal the mechanisms behind tumor metastasis and how to stymie it. But primary tumors still get the lion’s share of researchers’ attention . When a cancer cell spreads from a primary tumor to the brain, it immediately meets a formidable opponent: the astrocyte. These stalwart defenders protect against any would-be infiltrators that don’t belong in the brain. But metastasizing cancer cells can and do persist there—brain metastases occur in an estimated 20 to 40% of advanced-stage cancers. And new research suggests that those cancer cells may even be getting help from the astrocytes. Researchers are starting to reveal the elusive mechanisms driving metastasis, such as the liver metastasis (yellow) that is seen originating from primary colorectal cancer tumors in this 3D computed tomographic reconstruction scan. Image courtesy of Science Source/Phanie. When cancer cell biologist Joan Massague and his team cultured astrocytes together with lung or breast cancer cells, they found the cancer cells form physical channels called gap junctions running to the astrocytes (1). The team watched as red dye loaded into the cancer cells moved across the junctions, turning the astrocytes red. But that wasn’t all that passed through. The cancer cells sent over the molecule cyclic guanosine monophosphate–adenosine monophosphate (cGAMP), triggering a series of reactions within the astrocyte that ultimately led it to release inflammatory signals that support tumor growth. The cancer cell seems to parasitize the astrocyte, explains Massague, director of the Sloan Kettering Institute, the experimental research branch of the Memorial Sloan Kettering Cancer Center. The team next examined mouse models of cancer that were genetically engineered to lack receptors for cGAMP molecules. When they inoculated these mice with breast cancer cells that have a propensity to metastasize in the brain, they found the metastases that did form were smaller than in wild-type mice, suggesting …