Inserting a missing molecule in mice may shrink liver tumors or limit their growth By Jenny Lauren Lee Web edition : Thursday, June 11th, 2009

It’s a simple idea: Treat cancer by finding out what’s absent in a cancer cell and replacing it.

Experiments in mice suggest that inserting one small missing molecule could fight cancer without harming normal tissue, researchers at Johns Hopkins University in Baltimore and the Nationwide Children’s Hospital in Columbus, Ohio, report in a study in the June 12 Cell.

The molecule in this case is a small RNA chain known as a microRNA. MicroRNAs (abbreviated as miRNAs) are involved in a wide range of body processes relating to cellular differentiation and tissue growth. They run about 22 units long, but their size belies their influence — they help regulate hundreds of thousands of genes.

In the past decade, certain flavors of miRNA have been shown to be missing from cancer cells. Scientists have previously explored the idea that replacing the missing miRNAs might reverse the cancer, but not in a way that could lead to viable treatments, said Joshua Mendell of Johns Hopkins, one of the study’s authors.

“One of the things that distinguishes this work is that we used a clinically relevant delivery vehicle to replace a microRNA that’s missing,” Mendell says. The team used a harmless virus that acts as a sort of mail carrier to deliver the miRNA to the cells.

The researchers worked with mice made to develop tumors similar to those in human liver cancer. Most of the untreated mice developed cancers that nearly consumed their livers. But eight out of 10 mice receiving the miRNA had small liver tumors or none at all.

“It’s door-opening research” that will encourage others to move into the field, says George Calin of the University of Texas M.D. Anderson Cancer Center in Houston.

Mendell and colleagues focused on a particular strain of miRNA called miR-26a, chosen because it was absent in liver cancer cells but abundant in normal liver cells. “We thought that the tumor cells might be sensitive to the miRNA” but that the normal parts of the liver would not be harmed, Mendell says. Restoring the miR-26a stopped the cancerous cells from creating two molecules called cyclins that are used in cell replication, effectively preventing the cells from multiplying.

“Although microRNAs have been shown to play an important role in cancer pathogenesis, not too many reports have shown that altering a single microRNA can suppress cancer development in vivo,” comments Baohong Zhang of East Carolina University in Greenville, N.C. “This result has opened a novel strategy for cancer therapy.”

The study has great practical benefit, Calin says, because it shows potential for treating a specific type of cancer — hepatocellular carcinoma, or HCC, which accounts for 80 to 90 percent of all liver cancers.

Calin also says that this research suggests it may be possible to use different miRNAs as therapies for many diseases, not just cancers. MiRNAs have a wide variety of functions, and some have been linked with autoimmune disorders, diabetes and heart disease, he says.

Despite the promising results, Mendell says, there are a lot of hurdles to jump before this type of treatment could be used for people.

For one thing, the liver cancer in the mice is much more aggressive than most human liver cancers. The mouse livers were infested with multiple tumors; humans with HCC typically have only one. And since much is still unknown about how miRNAs work, this type of therapy might have unwanted consequences.

“I think we’re at the earliest stages of understanding,” Mendell says. “There’s more we don’t know than we know.”


Post a Comment