Scientists uncover how metastatic cancer cells plan their 'relocation'

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Washington, Jan 6 (ANI): Researchers at the Stanford University School of Medicine have discovered how metastatic cancer cells select their next site of infection.

Cancer biologist Amato Giaccia, PhD., the Jack, Lulu and Sam Willson Professor and professor of radiation oncology at Stanford, is the senior author of the research,

"Metastasis is not a passive process. 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," said Giaccia.

This means that cells plan ahead by first sending molecular emissaries to orchestrate a breach in the body's natural defenses. Blocking this cascade of events in mice hobbled the cells' migration and prevented the metastatic cancer that developed in control animals.

The researchers are hopeful that a similar tactic will be equally successful in humans.

Already, scientists know that certain primary cancers metastasize preferentially to other organs - for example, breast cancer often spreads to the lungs. This is in part due to the patterns of blood flow in the body.

Also, it was known that such future colonization sites, called pre-metastatic niches, harbour large numbers of cells derived from the bone marrow that somehow facilitate the cancer cells' entry.

However, they didn't know how the bone-marrow-derived cells were summoned, and what, if any, role the primary tumour cells played in site selection.

Thus, the researchers focussed on 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 called hypoxia that begins to occur when blood vessels fail to reach the inner cells of a growing tumour mass. Inhibiting LOX expression decreases tumour 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 new study, they found that blocking LOX expression in the mice not only prevented metastases, it 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, which in turn, secreted 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. Now we know that LOX goes to the target tissue and attracts CD11b and other bone-derived cells to the pre-metastatic niche. If the mouse data is transferable to humans, and we have reasons to think it will be, we really believe way may have found an effective way to treat human disease," said Giaccia.

The study is published in the latest issue of Cancer Cell. (ANI)

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