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New Research Offers Insight Into Metastatic Cancer

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What does a single cell inside a tiny roundworm about half the size of a pinhead have to do with human cancer? That single cell is providing valuable new clues into cancer's deadliest behavior—its ability to put down new roots and spread throughout the body.

"Metastasis accounts for most of cancer's lethality," said Dr. David Sherwood, an assistant professor of biology at Duke University. "It's the most essential step in cancer progression, but it's the least understood."

Dr. Sherwood has spent the last several years studying the mechanics of a single cell in the developing body of a one-millimeter long roundworm, called Caenorhabditis elegans. He specifically studies the anchor cell that connects the worm’s uterus with its vulva, a crucial step in ensuring fertility.

To establish this delicate connection, the anchor cell inside the roundworm reproductive organs must work its way through two layers of a dense barrier structure known as the “basement membrane.” The basement membrane lines most tissues, including the epithelial cells that are the hosts of many cancers in humans.

Because the anchor cell uses a series of molecular signals to create a stretched opening in the membrane, Dr. Sherwood and his colleagues believe the process used by cancer cells to invade new molecular tissues is essentially the same. This process could be a valuable new target in the effort to halt cancer’s spread via metastasis.

Since the late 1970s researchers have consider roundworms to be model organisms for this type of research. Not only are they abundant, inexpensive and rapidly multiplying, roundworms allow researchers to actually watch as the cell invasion occurs using newly-developed imaging technologies.

"In vivo, (within a living organism) you're dealing with individual cancer cells moving around the body. It is very hard to watch that," Dr. Sherwood said. "And then asking the cancer cell 'what genes are you using to do that?' is even more difficult."

There are about 100 genes that seem to prevent cell invasion, so Dr. Sherwood's team is searching for those that might be the most effective. A gene called SPARC, for example, is known to be over-active in cancer cells, enabling easier penetration of the basement membrane. The team is currently examining how this gene helps the anchor cell invade.

Dr. Sherwood said the research has produced more encouraging news: The molecules likely responsible for cancer metastasizing are outside the cell making them much easier to target with possible drug therapy.

The next step for Sherwood and his team is to understand how the cancer cell turns on its "invasiveness." The research isn’t there yet, but once this knowledge is better understood, scientists can turn their sights on applying these new clues to how best interrupt the cancer cell's potentially lethal behavior.

The National Cancer Institute has a fact sheet on Metastatic Cancer at http://www.cancer.gov

Azsunshinegirl, aka Lynette Summerill, is an award-winning journalist who lives in Scottsdale, Arizona. In addition to writing about cancer-related issues, she writes a blog, Nonsmoking Nation, which follows global tobacco news and events.

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