Study yields clues to why some tumors spread

CHICAGO (Reuters) - A small fragment of genetic material may mean the difference between an easily treated local tumor and an aggressive cancer that spreads throughout the body, U.S. researchers said on Thursday.

They found that when a bit of ribonucleic acid or RNA known as microRNA-101 goes missing, a protein called EZH2 starts to proliferate.

EZH2 has been linked with aggressive forms of breast, prostate, skin and bladder cancer, but until now it has not been clear what triggers overproduction of EZH2.

"What this study shows is why that protein is elevated in metastatic cancers," said Dr. Arul Chinnaiyan of the University of Michigan, whose study appears in the journal Science.

Chinnaiyan said EZH2 causes cancer to spread by shutting down other genes that keep cancer in check.

And he now thinks microRNA-101 or miR-101 is what keeps EZH2 from overproducing in cells. With this RNA bit missing, EZH2 causes cancer to spread.

"They are inversely associated. When one is up the other is down," Chinnaiyan, who is also a Howard Hughes Medical Institute investigator, said in a telephone interview.

"The cancer goes haywire when EZH2 is elevated and a bunch of other genes get turned off," he said.

To isolate what causes this protein to become elevated, Chinnaiyan and colleagues first turned to several computer programs. They came up with two suspects -- miR-101 and miR-217.

Then they went to work in the lab, testing to see if these molecules had any influence on EZH2. "Only miR-101 held up upon experiments," Chinnaiyan said.

When they introduced miR-101 into tumors in mice with high levels of EZH2, levels of this cancer-causing protein fell, and tumor growth slowed.

Chinnaiyan said in some cancers, miR-101 gets deleted from the genome, giving rise to an overproduction of EZH2 and metastatic cancer.

For patients, the discoveries may be useful on two fronts.

"It potentially could be used as a biomarker. Loss of miR-101 could portend metastasis of cancer," Chinnaiyan said.

And knowing a cancer is likely to spread could guide the way doctors treat it, he said.

It also could lead to new therapies that restore miR-101, giving the body back a natural defense against the spread of cancer.

Chinnaiyan said currently there are few good ways to deliver microRNAs to human cells, but many companies are working on this.

If they succeed, it may be possible to arrest the spread of certain forms of cancer. And that could save lives.

"It's really the metastasis that is lethal to patients," Chinnaiyan said.

(Editing by Maggie Fox and Vicki Allen)