Pressure keeps cancer in check

Physically confining malignant cells prevents runaway growth

SAN FRANCISCO — Putting the squeeze on lab-grown tumor cells makes them behave like healthy ones, a new study shows. The discovery won’t lead to treatments that poke and prod tumors in patients, but it might help researchers develop new drugs that keep mutated cells from growing out of control.

UNDER PRESSURE Breast cancer tumors (left) form normal-looking structures (right) after brief compression, researchers at the University of California, Berkeley have discovered. G. Venugopalan/UC Berkeley

Breast cancer cells suspended in gel and then briefly compressed form orderly balls, just like normal breast cells do when squeezed, Gautham Venugopalan, an engineer and cell biologist at the University of California, Berkeley, reported December 17 at the annual meeting of the American Society for Cell Biology. “We’re not adding any drugs. We’re not changing any genetics,” Venugopalan said. “All we’ve done is basically kicked them and said, ‘you need to be normal now.’”

The cells still carry the genetic changes that led them to become cancerous, but after the big squeeze they act as if they are healthy.

A protein called E-cadherin that sits on a cell’s surface and helps form close bonds with neighboring cells is necessary for the return to good behavior, the researchers discovered. When Venugopalan added antibodies that interfere with the protein before putting the pressure on tumors, the tumor cells remained cancerous.

The result is surprising, said Mark LaBarge, a cell biologist at Lawrence Berkeley National Laboratory who was not involved in the study. Previously, researchers had shown that growing precancerous cells in stiff three-dimensional gels brings out the cells’ malignant side. So compressing cells might be expected to stiffen things and encourage bad behavior. Instead, pressure seems to stimulate healthy cellular processes.

Compression probably won’t be used to treat cancer in the clinic, Venugopalan said. Squeezing cells in lab dishes is far different than compressing tissue in people. But if the researchers can learn what pressure does to make tumors behave, they may be able to devise drugs that turn on the same processes. “You don’t necessarily have to kill a cancer cell,” Venugopalan said, “you just need to make it behave noncancerous.”

Tina Hesman Saey is the senior staff writer and reports on molecular biology. She has a Ph.D. in molecular genetics from Washington University in St. Louis and a master’s degree in science journalism from Boston University.

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