Why does breast cancer sometimes come back, even after what seems like successful treatment and periods of being cancer-free? A researcher at UW-Milwaukee is investigating the fact that some cancer cells go dormant to hide from radiation treatment – only to wake up later and return, sometimes even stronger.

Between 40% to 50% of breast cancers return after a period of remission. One reason may be that certain cancer cells survive treatment by slipping into a dormant state. These “sleeping” cells aren’t actively growing or dividing, which makes them harder for radiation and chemotherapy to detect and destroy.

Qingsu Cheng, assistant professor, biomedical engineering, believes a certain kind of cell called a fibroblast might be helping cancer cells enter and later emerge from this hidden state.

Cheng will dig deeper into whether fibroblasts facilitate the cancer cells’ work-around during radiation exposure with funding from the Shaw Scientist Award from the Greater Milwaukee Foundation.

The annual award supports research in biochemistry, biological sciences, and cancer research by providing $200,000 in funding to early career scientists at each UW-Madison and UW-Milwaukee. The fund was established by the late James D. and Dorothy Shaw, donors to the Greater Milwaukee Foundation.

Cancer’s effect on fibroblasts

Fibroblasts are usually part of the body’s healing system. But in cancer, tumors can hijack fibroblasts, reprogramming them from defenders into promoters that help cancer grow, spread, and resist treatment.

“We know some parts of the story, but not all of it,” Cheng said. “If we can stop cancer cells from going dormant in the first place, we might reduce the chance of the cancer coming back after successful treatment.”

Radiation is a powerful tool in the fight against cancer because it can reach deep into tissues and destroy cancer cells. But some cells survive. Cheng wants to know: What exactly happens at the cellular level when radiation penetrates the tumor’s microenvironment? And are fibroblasts somehow being recruited to help in the process of dormancy?

Other factors

His lab will also explore what revives these hidden cells and how the body’s circulatory system may be involved in helping cancer cells spread or resist treatment during radiation exposure.

If radiation plays a role in these processes, then a logical related question for Cheng is, “Does a patient’s lifetime exposure to low-dose radiation — like from medical scans or mining work – fit into the puzzle?”

Some people are more susceptible to the radiation than others, but little is known about why. Findings of this project could provide clues.

The project also will look at high-density breast tissue which tends to contain more reprogrammed fibroblasts and is a known risk factor for developing breast cancer. It may also play a role in why some cancers return after treatment.

“By understanding the microenvironment around tumors, we can start to identify new targets for treatment,” Cheng said. Once those targets are known, he plans to test potential drugs or therapies to stop cancer from hiding.

Yin Wang, associate professor, civil & environmental engineering, and Xiaoli Ma, associate professor, materials science & engineering, are investigators on a two-year grant from the U.S. Department of Defense to improve the efficiency and precision of removing PFAS compounds from water.

In the project, funded at nearly $250,000, the researchers will focus on modifying a clay-like mineral called “layered double hydroxide” (LDH). Shangping Xu, UWM associate professor, geosciences, is also on the research team.

PFAS (per- and polyfluoroalkyl substances) are synthetic chemicals used in a wide variety of products, from stain-resistant carpets to firefighting foam. Called “forever chemicals” because of their persistence in the environment, PFAS compounds are linked to harmful health effects – even at very low concentrations.

“There are methods of removing some PFAS compounds, but we need more efficient and more cost-effective ways,” Wang said. “One challenge is to find a way to remove more from drinking water to make sure it meets the recent regulations.”

Because even a small amount is harmful, almost all the chemicals must be removed to meet the EPA’s recent limits set for six PFAS compounds.

Using electrostatic interactions to attract and repel

LDHs are promising adsorbents, materials that collect dissolved or minimal amounts of contaminants like a molecular magnet. The layers of LDH carry a highly positive charge on their surfaces, attracting the negatively charged PFAS ions, Wang said. And the layered structure of LDH may increase the area where adsorption occurs, boosting the materials effectiveness.

Relying on this electrostatic attraction alone, however, may not suffice, Wang said.

To take it a step further, the team will tweak the material so it becomes hydrophobic, or water-repellent.

The researchers have seen this interaction before. Once PFAS filters reach the end of their usefulness, the accumulated PFAS on them must be removed so that they can be recycled. Currently, an organic solvent is used to do this because PFAS is hydrophobic.

This work could lead to a powerful new way to clean contaminated filters that is safer for the environment.

“We are trying to see if we can change the interaction between LDH filter material and the PFAS so that a similar hydrophobic interaction happens,” Wang said, “and more importantly, if the LDH filter material can be regenerated without organic solvents.”

The biggest obstacle

The research builds on Wang and Xu’s earlier work developing powdered LDH adsorbents licensed by a national manufacturer through UWM’s Water Equipment and Policy Center.

The researchers hope the work will give insight into one of the biggest roadblocks in PFAS cleanup: military installations where fire-fighting foam was used for decades, and the contaminant has settled in surrounding soil. At these sites, just below the water table, the PFAS can be in concentrations thousands of times higher than in water reservoirs.

Researchers continue to look for solutions that more selectively remove greater amounts of PFAS in these locations.