NU study might improve breast cancer treatment

Joanna Allerhand

A recent study by Northwestern researchers might help doctors predict which breast cancer patients are least likely to survive.

Women whose breast tumors expressed high levels of the protein alphaB-crystallin had a lower rate of survival, said Vincent Cryns, who led the study at NU’s Feinberg School of Medicine.

The implication is that the presence of the protein might be a predictor of a patient’s chances under traditional treatment.

“Knowing who will and who won’t respond could be useful in terms of moving patients to other experimental or investigative treatments,” Cryns said.

Eventually, treatments can be developed that are designed specifically to benefit patients whose tumors express alphaB-crystallin.

The protein has been shown to activate a molecular pathway that leads to uncontrolled cell growth, which is one characteristic of tumors. Administering a drug that blocks this pathway might be one way of reducing the effects of alphaB-crystallin and improving the prospects of the patients, said Jose Moyano, a post-doctoral fellow in Cryns’ lab.

Investigation into the effects of the protein began by attempting to prove that alphaB-crystallin impedes cell death and thus promotes the unrestrained growth of cancer cells.

But the exact role of the protein in making the cancer more deadly is still unknown, Cryns said. It might cause the cancer to become more aggressive, or its expression could inhibit the response of the patient to traditional therapies, he said.

About 411,000 women worldwide each year die of breast cancer, and it is the most frequently diagnosed cancer in women.

Cryns and his team analyzed a panel of more than 400 breast cancer patients and found that the alphaB-crystallin protein was expressed in 11 percent of the tumors. But “before it can be clinically useful, (the link) has to be validated in larger studies,” Cryns said.

Under normal conditions, alphaB-crystallin assists other proteins in times of stress, and levels of it range from low to non-existent. But in cancer cells the protein is found at high levels and at all times, Cryns said.

Over-expression of the protein is not specific to breast cancer. Evidence of its increased presence exists in a variety of cancers, including brain and kidney cancer. Cryns said.

Researchers are uncertain whether an already present cancer leads to increased levels of the protein or if alphaB-crystallin itself acts as the trigger and stimulates other cancer-causing agents.

“We are currently looking into (which comes first),” Moyano said.

Cryns’ lab uses an advanced technique to grow breast cells in a three-dimensional environment that allows the cells to mimic a more realistic situation than was possible by growing cells in single layers.

The cells eventually form a structure similar to the mammary gland found in an actual breast, Moyano said.

Moyano then introduces alphaB-crystallin to the non-cancerous cells.

“What we have seen is that alphaB-crystallin, with these cells grown in this environment, the gland structure is disrupted and they express cancer-like properties,” he said.

Most labs do not use this 3D technique because it is technically challenging, Cryns said.

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