Cancer Cells Sprout Tiny 'Feet'

Before cancer cells wander away from their original site to other parts of the body, the cells develop “feet” called invadopodia, new research shows. If doctors can cut cancer cells off at the knees, they may be able to stop the disease from spreading.

In a study recently published in Cell Reports, researchers watched with high-resolution time-lapse imaging as dyed cancer cells tried to escape from the bloodstream of chicken embryos and mice to establish themselves in a new location. That process, called metastasis, is why a breast cancer patient may later find herself with cancer in her bones, for example.

“We started to see invadopodia being formed. They form these tentacle-like fingers,” said senior study author John Lewis, an oncologist at the University of Alberta in Canada.

The researchers watched as the tentacles fumbled around to find a spot between two blood vessel cells. The tiny tentacles then reached out and hauled the cancer cell out of the blood vessel.

“Being in a blood vessel is a horrible environment for cancer cells — there’s all kinds of immune activity. To survive they need to get out quickly,” Lewis said.

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John Condeelis, a microbiologist at the Albert Einstein Cancer Center at Yeshiva University who has published studies on invadopodia, said the same “doorway” forms between the cancer cell and the blood vessel as it enters and as it leaves.

“The door swings both ways and the cells can cross in or out of the vessel,” he said.

New Insight into How Cancer Spreads

The findings add to a growing agreement among scientists that cancer cells need invadopodia to spread. The feet first allow them to break through the rigid structures that hold cells in place, other studies have shown. Then they help the cells anchor themselves in their new location, Lewis’ study found.

All types of cancer observed in the new study, including melanoma and breast cancer cells, used invadopodia to spread. And when researchers prevented the cells from sprouting feet, the cancers did not spread.

In other words, without feet, the cells have to stay put, where doctors can attack them with surgery, chemotherapy, and radiation.

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Hope for New Treatments

The next question for researchers is how best to stop invadopodia from forming in the first place.

Cancer cells use proteins called MT1-MMP, cortactin, Tks4, and Tks5 to build their foot-like appendages. Lewis and his colleagues blocked production of these proteins using gene-silencing RNA. RNA is being used in a similar way in clinical trials to potentially combat cancer and genetic diseases.

While the other proteins serve a number of functions, Tks5’s sole purpose is to make invadopodia. That suggests that stopping production of Tks5 might not generate many side effects.

The researchers also tried saracatinib, a drug already in clinical trials as a cancer treatment, as way to cripple the cancer cells.

Condeelis has focused instead on blocking the signal that tells cancer cells it’s okay to form invadopodia. That’s what’s exciting about this new research on how cancer travels: For every step along the way as a cancer cell forms feet and marches toward metastasis, there’s a chance for doctors to interrupt the process.

Of course, every interruption researchers devise will have to work safely in clinical trials. The process will whittle down the wide range of possibilities this early research has revealed.

“There’s a number of strategies and therefore a number of drug interventions that could be tried. It really comes down to what the patient will tolerate. You might have good efficacies for all of them, but the patient will only tolerate one of them, so that’s the one you have to go with,” Condeelis said.

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