New founding in cancer cell metastasis new hope for primary cancer

WASHINGTON, Jan. 5 (Chinese media) -- 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.