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Engineer Tackles Cancer Metastasis in Brand New Way

Shelly Peyton, an Assistant Professor of Chemical Engineering and the Barry and Afsaneh Siadat Career Development Faculty Fellow at the University of Massachusetts Amherst, has received a five-year, $2.4-million grant from the National Institutes of Health (NIH) to attack the deadly problem of breast-cancer metastasis in an entirely new way. “What we’re trying to understand is why breast cancer doesn’t spread randomly,” explains Peyton about her project for the NIH Director’s New Innovator Award program. “It almost always ends up in a few areas of your body, and that’s what makes it so deadly."

She adds that "Ninety percent of breast cancer deaths are due to metastasis. So the ability of breast cancer to spread to your brain, your lungs, your bone, your liver, and take over those organs, that’s the real danger.”

This crucial and potentially fatal problem with breast cancer has remained a mystery for more than a century: Why do different kinds of breast cancer cells tend to spread to specific organs? That’s the killer. Peyton actually engineers authentic replicas of brain, lung, bone, liver, and other organs from synthetic polymers in her lab and will use these “tissue mimics” to test her new theory for why breast-cancer cells metastasize to certain organs. Then she will study how to block cancer cells from doing so. She is the only engineer in the world employing this promising new method.

Peyton’s novel hypothesis about why breast-cancer cells spread to certain organs is that, first, they signal to stem cells specific to the brain, lungs, liver, bone, and other tissues and thereby activate them within their corresponding organs. Ironically enough, the main purpose of these stem cells is to repair inflammation or injury in the organs. However, in the presence of cancer elsewhere in the body, these injury-fighting stem cells instead turn into cancer cultivators. They remake the tissue of their respective organs into favorable environments to which breast cancer cells can migrate and live.

As Peyton says, “I propose that stem cells which reside in the local tissue and respond to injury are activated by tumor-released factors and remodel the surrounding tissue, creating a favorable soil before the arrival of metastatic tumor cells.”

Anyone who has ever seen the Sci-fi thriller Invasion of the Body Snatchers can understand Peyton’s new theory. In that film, alien beings plant seed pods on earth which grow into exact replicas of real human beings. When all these seed pods replace their human look-alikes, they quickly cultivate a favorable environment for the alien invasion. In Peyton’s hypothesis, breast cancer uses a similar modus operandi, with stem cells acting as alien seed pods.    

Peyton will research this crucial issue by coupling her engineering expertise in biomaterials development, stem cell biology, systematic measurement of biological processes and response, and statistical modeling.

Basically, what Peyton is doing in her lab is manufacturing disease models ex vivo, or outside the body. By using synthetic materials to build brain, lung, bone, liver, or other tissues, she can then introduce breast cancer cells to test how they interact with the various organs. Peyton expects this approach to reveal why breast-cancer cells migrate to specific tissues, a process which she believes is intimately linked to the stem cells released by the tumor cells into those respective organs.

Peyton explains that in a sense what these stem cells are doing is remodeling the secondary tissues such as the brain, lungs, bone, or liver. They’re breaking down certain proteins, replacing them with others, making each organ into a chemically and mechanically favorable environment for cancer cells to grow in and thrive.

“There are stem cells all over your body,” Peyton explains, “neural stem cells in your brain, lung stem cells in your lung, skeletal stem cells in your muscle, and all those stem cells can be activated in response to inflammation. Whenever you have injuries or inflammation, it triggers these stem cells. In the absence of cancer, their job is to respond to injury and help heal it. But in the presence of cancer, they are actually paving the way for metastasis.”

The goal of Peyton’s NIH proposal is to use her lab-engineered organs, exposed to the influence of cancer tumor cells, to study this “metastatic cascade of events,” as she calls it.

After Peyton tests her theory both in her “tissue mimics” and in mice, she will look at the specific signals transmitted by cancer cells to various stem cells. Then, in what she hopes will be some kind of a coup de grâce for this kind of metastasis, Peyton will attempt to block those signals and prevent the cancer cells from migrating from the tumor site in the breast to target organs such as the brain, lungs, bone, or liver.

“That’s our pathway for a new therapeutic,” as Peyton declares.

In the past year, Peyton’s very promising new approaches to breast cancer and cardiovascular disease have also been supportedby a $590,000 National Science Foundation grant, a $198,000 grant from the American Heart Association, and $240,000 from the Pew Charitable Trusts, when it named her one of the 22 Pew Scholars in the Biomedical Sciences nationwide. (October 2013)

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