The study of a protein, critical in causing asthma, allergies and other diseases, has led scientists at Benaroya Research Institute at Virginia Mason (BRI) to discover a new strategy for stopping breast cancer.
BRI researchers Emma Kuan, PhD, and Steven Ziegler, PhD, have pinpointed how the protein, called thymic stromal lymphopoietin (TSLP), causes breast cancer tumors to survive and grow. Even more significant, the researchers showed that blocking TSLP can significantly inhibit the growth of breast tumors and halt metastasis to the lungs. This discovery opens the door to new strategies that could stop breast cancer tumors from growing and spreading. It may also be applied to other tumors that involve TSLP.
“Breast cancer becomes especially dangerous once it spreads to other parts of the body,” Dr. Kuan says. “Our work suggests that blocking TSLP could prevent this from happening and potentially save the lives of women worldwide.”
The research was published recently in Nature Immunology. TSLP was discovered 15 years ago by the Ziegler Laboratory, as well as other labs, to initiate the inflammatory cascade that leads to the development of asthma, allergies and other diseases.
How TSLP Helps Tumors
Researchers had previously found elevated TSLP levels in several different tumor types, but its role in tumor biology was unclear. Drs. Kuan and Ziegler solved this mystery by using preclinical models to investigate what happens to breast cancer tumors when TSLP is taken away.
Their research revealed that the tumors didn’t grow nearly as large – or metastasize nearly as much – when they didn’t have access to TSLP. In fact, the breast cancer cells died without access to TSLP, resulting in markedly smaller tumors and a lack of lung metastases, compared to tumors where TSLP was present.
“The tumors can get started without TSLP, but they need it in order to stay alive and metastasize through the body,” Dr. Ziegler says.
Hijacking Immune Cells
Once the researchers determined that TSLP was critical, they set out to uncover how it worked – and became the first to discover that tumors turn immune cells into accomplices that express TSLP. Importantly, the researchers found that the same cells that make TSLP in the models also make TSLP in human breast cancer patients, and human breast tumor cells respond to TSLP in the same way.
Stopping Tumor Growth
When Drs. Kuan and Ziegler used an antibody to block TSLP, it stopped tumors in their tracks – even when they had already started growing. Within six weeks, the tumors had shrunk significantly, more of their cells were dying and they had stopped spreading to the lungs. This suggests that anti-TSLP therapy could work in human patients with existing tumors.
“Blocking TSLP could potentially contain not just breast cancer, but many other tumors that have elevated TSLP – including pancreatic cancer, cervical cancer and multiple myeloma,” says Dr. Kuan.
A drug that blocks TSLP has already been developed and initial trials have shown that it’s safe in patients with asthma, so scientists are hopeful clinical trials could be launched for cancer patients in the relatively near future.
“We’re currently working on a better way to block only the TSLP that helps tumors,” Dr. Kuan says. “and we are really hopeful that this could become a viable strategy for containing tumors long-term, without interfering with TSLP in other healthy cells.”
New Cancer Biorepository
For their research, Drs. Ziegler and Kuan used samples from BRI’s new biorepository, the Virginia Mason and Benaroya Research Institute Tumor Repository (VM BRITE). The biorepository houses the medical history and blood and tumor samples of research participants with a variety of cancers.
“As BRI studies the immune system and tries to understand why it veers off course, we learn how it relates to other diseases such as cancer,” says BRI President Jane Buckner. “We want to pursue these discoveries to improve the lives of people with autoimmune diseases, cancer and hopefully many other diseases.”
May 17, 2018
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