Wolf in sheep's clothing: breast cancer cloaks itself in brain proteins to invade the brain
March 14, 2017 | by Denise Heady
More women than ever are surviving breast cancer — 2.8 million in the U.S. to date — only to die of secondary brain tumors years after they’ve been declared cancer-free. This is particularly true for patients with the breast cancer subtype HER2-positive. Approximately 40 percent of all women with HER2-positive breast cancer (around 20 percent of all breast cancers) will develop brain metastases.
Now City of Hope researchers have discovered how this happens.
Breast cancer cells act as a wolf in sheep’s clothing, wrapping themselves in reelin — a protein typically found only in the brain — that allows the cells to disguise themselves, avoiding a system in the brain designed to detect enemy cells. From these disguised cells, new deadly brain tumors form.
“The cells are essentially able to act as spies that look like citizens,” said City of Hope dual-trained neurosurgeon and scientist Rahul Jandial, M.D., Ph.D. “They release a mesh of protein and escape the brain’s natural defense weapons, causing tumors to grow in the brain.”
Understanding these mechanisms is an important step in developing new therapies to treat brain cancers — especially for metastatic cancers. Metastases are responsible for 90 percent of all cancer deaths, and patients diagnosed with brain metastases only have a 20 percent chance of surviving a year after diagnosis.
Jandial, associate professor in the Division of Neurosurgery, recently published his findings, which are available online and slated for the upcoming print publication of the Clinical & Experimental Metastasis, the journal for the Metastases Research Society.
“I wanted to understand why women with HER2-positive breast cancer have higher rates of brain metastases than women with other breast cancer subtypes and, in turn, find their biological Achilles' heel to develop new medicines.”
After performing brain surgery, Jandial and his team took leftover tissue samples and compared them to breast cancer tissue removed from mastectomies in the same women. They compared the expression of proteins and found that reelin expression was low in primary breast cancer tissue. However, its expression was significantly higher in HER2-positive breast cancer metastasizing to the brain.
Too many women — and their physicians — are unaware of this risk. To make matters worse, current treatments for these tumors are limited, poorly effective and have a poor prognosis.
"My goal as a physician is to help patients diagnosed with brain metastases live longer. To do that, we need to identify the ways biology promotes cancer growth to the brain and interrupt that process, and hopefully, find a better approach to treating these tumors. This is one step in achieving that goal.”
Collaborating authors include Cecilia Choy, Ph.D., Danielle M. Levy, Ph.D., Mike Y. Chen, M.D., Ph.D. and Khairul I. Ansari, Ph.D., all of Beckman Research Institute of City of Hope.
Funding for this research is supported by Department of Defense Grant BC142323, The Margaret E. Early Medical Research Trust, National Institutes of Health Grant K12 CA001927-16A1 and National Cancer Institute Grant P30 CA033572.
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