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Patricia Keely - Disrupting the Cancer 'Highway'

 

 

High-Tech Tools Show the Way Out

 

On the University of Wisconsin campus lies the Laboratory for Optical and Computational Instrumentation. Known more commonly as LOCI, lab participants like Patricia Keely, PhD, not only use but also develop novel imaging techniques.

 

With her skilled lab team, some high-tech instruments, and 20-plus years of experience, Keely is diving into another day of research with the aim at making an impact.

 

The team is focusing on breast cancer metastases and its relation to breast tissue density. The findings: In a number of cases, “highways” of dense tissue, primarily consisting of collagen, are guiding tumor cells out of the original tumor site and into the rest of the body. The patterns in collagen that make up these highways are so consistent that they’ve been dubbed as “collagen signature.”

 

Mammary epithelial cells cultured in 3D collagen gels differentiate into tubule structures. This differentiation is disrupted when cells are cultured in dense 3D collagen gels, providing a model system for understanding the molecular underpinnings for cellularresponses to matrix density.“One of the things we’re looking at right now is whether we can use this marker to help us tell the difference between patients who are likely to relapse and those who aren’t,” said Keely, who leads the Tumor Microenvironment Program at the UW Carbone Cancer Center and serves as director of the Molecular and Cellular Pharmacology Graduate Program at the University of Wisconsin School of Medicine and Public Health.

 

Using mouse models, her team had a medium in which it could directly manipulate the potential tumor environment and determine how increased amounts of connective tissue affected the cancer’s growth and spread.

 

“With the changes we found in the collagen in the mouse model, we were able to use a set of human patient tissue samples, the kind of samples a pathologist looks at, and found the same changes in the collagen. We were able to look at how those changes correlated to patient outcomes across 200 patients,” she said.

 

A Personal Connection

 

Each of those patient samples rings home in some way for doctors and researchers alike. They’re from a patient. A mother. An uncle. Maybe a neighbor or coworker. It doesn’t take six degrees of separation to find these connections; for nearly 13 million people worldwide, all it takes is a mirror to see someone who has battled or is battling cancer. Keely takes these connections to heart. After all, she’s is not only a researcher.

 

Mouse mammary carcinoma cells (blue) invading into the surrounding collagen stroma (green/yellow) in fresh, unstained, unfixed tissue, and visualized by fluorescence lifetime imaging microscopy.

“I was originally diagnosed with a form of lymphoma when I was a college student and I went through radiation and chemotherapy,” she said.

 

Perhaps too close to the subject, she decided then that cancer research wasn’t something Keely wanted to tackle. She stayed away as best she could, but over time, she became very interested in cancer as a biological problem that really needed to be solved.

 

“Recently, I had esophageal cancer that was a direct result of the radiation therapy that I had 20 years ago,” she said. “From that, I’ve actually become more motivated now to make our cancer research be related directly to helping patients ... to try to come up with diagnostics or hopefully a cure ... something that will help people.”

 

Intervention in Mind

 

Springing from the rather basic research question of how connective tissue relates to tumor formation, the team identified very specific changes that are functionally related to cells migrating out on the collagen. With outcome and prediction understood, now it’s back to the mouse model to find ways to disrupt those dangerous cellular highways.

 

“It’s still quite a ways to go from treating breast cancer in a mouse to taking these same agents and treating cancer in humans; however, one of the things that is very exciting is recently we found that a very common drug used to treat arthritis actually helps prevent some of the changes we see in collagen,” said Keely. “If we can use a drug that’s already approved for another use, then that step to helping prevent the spread of their breast cancer is a lot shorter.”


Patricia Keely - Disrupting the Cancer 'Highway'

Last updated: 01/28/2015
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