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Dodging a Bully

Ovarian cancer cells use brute force to permeate tissue

Ovarian cancer video

Invaders in Action: Watch ovarian cancer cells plow their way through tissue.

A team led by Joan Brugge, chair of the HMS Department of Cell Biology, has shed light on how ovarian cancer spreads. In a paper published in the July issue of Cancer Discovery, Brugge and colleagues found that ovarian cancer cells act like bullies, using brute force to plow their way through tissue and colonize additional organs.

“This is the first time that mechanical force has been implicated in the spread of ovarian cancer,” says Brugge, who is also the Louise Foote Pfeiffer Professor of Cell Biology at HMS. “While this research is still preliminary, we are building a foundation for the development of treatments based on a robust understanding of the disease.”

The ovaries are located in the peritoneal cavity, whose lining, the peritoneum, is topped with a layer called the mesothelium.  After an ovarian tumor develops, clusters of cancer cells are released into the peritoneal cavity. Each cluster floats around until it encounters the lining of the cavity. It attaches to the lining, spreads out, and launches an invasion into the mesothelium. Brugge’s team determined how ovarian cancer cells get through the mesothelium to colonize organs on the other side.

The researchers identified three critical players in the invasion process—integrin, talin, and myosin, proteins known to play a role in cell movement. Integrin protrudes from the cancer cells and grabs hold of scaffolding surrounding the mesothelium. Myosin, which is a motor, pulls on integrin through talin. As a result, the cancer cells gain traction and force mesothelial cells out of the way.

“Eventually, it might be possible to prevent or reverse this invasion process,” says Brugge. “We hope that our work will inform such treatments in the future.”

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