Cancer's break-in tools possibly identifi...( A single cell in a 1-millimeter nema...),Health

A single cell in a 1-millimeter nematode worm is providing valuable new clues into cancer's deadliest behavior -- its ability to put down roots in new tissues after spreading throughout the body.

Duke University biologist David Sherwood has spent the last several years studying the mechanics of a single cell in the developing body of a worm called Caenorhabditis elegans. It's 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.

In a paper appearing online Aug. 17 in the journal Developmental Cell, Sherwood and colleagues describe how the nematode's anchor cell uses a series of molecular signals to create a stretched opening in the membrane. They believe the process is essentially the same as the one cancer cells use to invade new tissues.

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

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.

The abundant, cheap, rapidly multiplying worms -- and their basement membranes --
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