Little is known about how metastatic cancer cells choose where to relocate but researchers at the Stanford University School of Medicine have found a relationship between a protein and the process.

"Metastasis is not a passive process," said Amato Giaccia, a professor of radiation oncology at Stanford and the senior author of the research to be published in the Jan. 6 issue of Cancer Cell, according to a news release by Stanford's medical center.

"Cells don't just break off the primary tumor and lodge someplace else. Instead, the cells actually secrete substances to precondition target tissue and make it more amenable to subsequent invasion," he said

Scientists have known that certain primary cancers metastasize preferentially to other organs. They also have known that such colonization sites, called pre-metastatic niches, harbor large numbers of cells derived from bone marrow that somehow facilitate the cancer cells' entry. What they did not know is how the bone-marrow-derived cells were summoned, and what, if any, role the primary tumor cells played in site selection.

Giaccia and his colleagues turned their attention to a substance that they had previously shown to be involved in metastasis: a protein called lysyl oxidase, or LOX.

LOX expression increases in cancer cells deprived of oxygen -- a condition known as hypoxia that begins to occur when blood vessels fail to reach the inner cells of a growing tumor mass. Inhibiting LOX expression decreases tumor cell invasion and metastasis in the lungs of mice implanted with human breast cancer cells.

The researchers wanted to know how LOX affected metastasis. In the current study, they found that blocking LOX expression in the mice not only prevented metastases but also kept the bone-marrow-derived cells necessary for niche formation from flocking to the site.

When LOX was present, it accumulated in the lungs of the mice and was associated with one particular type of bone-marrow-derived cell known as a CD11b cell. CD11b cells, in turn, secret a protein that breaks apart collagen and provides a handy entry point for the soon-to-arrive cancer cells.

"We've never really understood before how normal tissues are modified to allow metastases to target and successfully invade them," said Giaccia.

"Now we know that LOX goes to the target tissue and attracts CD11b and other bone-derived cells to the pre-metastatic niche," he said.

"If the mouse data is transferable to humans, and we have reasons to think it will be, we really believe we may have found an effective way to treat human disease," the researcher said.