Worm Study Holds Clue in the Study of Invasive Cancer

by Savitha C Muppala on Aug 20 2009 11:37 PM

A single cell's behaviour during the development of the reproductive tract in the C. elegans worm is providing scientists with significant insights into cancer's deadly ability to put down roots in new tissues after spreading throughout the body, say researchers.

David Sherwood, a Duke University biologist, has spent several years studying the mechanics of a single cell in the developing body of the worm.

He points out that it is called the anchor cell, and one of its jobs is to connect the developing animal's uterus with its vulva, a crucial step in ensuring the worm's fertility.

To establish this slender connection, the anchor cell must work its way through two layers of basement membrane, a dense, sheet-like barrier structure lining most tissues, including the epithelial cells in humans that are the hosts of many cancers.

Writing about their study in the journal Developmental Cell, Sherwood has described how the nematode's anchor cell uses a series of molecular signals to create a stretched opening in the membrane.

He and his colleagues believe that the process is essentially the same as the one that cancer cells use to invade new tissues.

The researchers say that, together, these molecules-called integrin and netrin-may be a valuable new target in the efforts to halt cancer's spread via metastasis.

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

To push a hole through the basement membranes, the worm's anchor cell forms several lancet-like points, called puncta. They look remarkably like a structure seen in cancer cells called invadopodia that are believed to have the same function, but modeling this part of metastasis in the lab has proven impossible so far because nobody has figured out how to make a basement membrane in a dish.

Sherwood says that the abundant, cheap, rapidly multiplying worms and their basement membranes enabled his team to do a variety of experiments to narrow down the genes and molecular signals in play.

He said that with the aid of newly developed imaging technologies, he and his colleagues could actually watch as the cell invasion occurs.

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

He says that the latest set of findings suggest that integrin helps the anchor cell orient itself toward the basement membranes, and that it also directs netrin to build the puncta in the proper place to ease an opening through.

The researcher says that what is even more interesting about the two molecules it that they are outside the cell, which makes them easier to target with possible drug therapy.

Sherwood says that there are about 100 genes that seem to prevent cell invasion, and that his team is searching for those that might be the most effective.

He has revealed that the group is presently examining how a gene called SPARC, known to be over-active in cancer cells, helps the anchor cells invade.

He said they would like to know how the cell turns on "invasiveness" to understand the best way to interrupt this potentially lethal behaviour.