Mammary cell protein able to fight cancer cells

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In an important step forward in the fight against breast cancer, researchers from UC Irvine and the Lawrence Berkeley National Laboratory have found that a protein naturally secreted by healthy mammary cells can stimulate death in cancerous tissue.

The research team, headed by Mina Bissell, a distinguished scientist in the Life Sciences Division of Berkeley lab, discovered that because receptors for the cytokine Interleukin 25 - a protein known for its role in the immune system's response to inflammation - are present on malignant tissue but not on healthy cells, IL-25 can bind to and attack cancerous cells while leaving healthy mammary tissue intact.

The team published their findings in the April 13 issue of Science Translational Medicine.

"The major function (of IL-25) people have studied so far is its role in inflammatory response," said Saori Furuta, a postdoctoral fellow at Berkeley lab and co-author of the study. "It's actually highly expressed in immune cells in response to stress or some diseases or pathogens."

After the researchers stained 69 samples of both cancerous and noncancerous breast cells with IL-25 receptor antibodies, the cancerous cells were mainly the only ones left stained, revealing that IL-25 receptors are specific to tumors and can be used to indicate cancerous tissue.

The reason breast tumors often continue to grow despite the presence of IL-25 that is secreted by healthy cells is because there is not enough of the protein in the vicinity.

Additionally, IL-17B, a protein present in tumors, can also bind to the IL-25 receptors and provides a "gross stimulant effect" that actually helps the tumor to grow, said study co-author Irene Kuhn, lab manager at the Bissell lab.

However, their research suggests that IL-25 binds more easily with the IL-25 receptor, and that if it were to be injected into the cell, it would bind to the receptor more easily than IL-17B, thus inhibiting growth.

According to the study, the researchers tested the potency of IL-25 on tumors growing in mice, and found that at the end of one month, tumors injected with IL-25 were on average three times smaller than those in the control group injected with a saline solution. Additionally, an examination of the treated mice at the end of the month showed that the treatment appeared not to cause side effects.

"One of the windfalls of working with something that's a natural product of the body to begin with is that it's unlikely that it would have much cytotoxicity or side effects," Kuhn said. "That said, we don't yet know anything about what dose would need to be achieved to have a therapeutic effect."

The study could have broad implications for treatment development, which is often difficult because breast cancer has a number of subtypes that respond differently to different drugs, according to Alexander Borowsky, an associate professor of pathology and laboratory medicine at UC Davis and a visiting senior scientist at Berkeley lab. IL-25 treatment could be applicable to a large subset, Borowsky said.

The time it would take to develop a therapy would depend on a number of factors, including the outcome of later clinical trials, Furuta said in an email.

"Optimistically, if everything goes well, I would estimate five to 10 more years until this method becomes a working therapy," she said.

She added that IL-25 could potentially be used to treat other cancers, including pancreatic, prostate and liver, but that they do not yet know whether non-breast tissue would react in the same way.

Contact Emma Dries at [email protected]

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