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Unraveling the Cancer Cell

Researchers at The University of Texas at Austin’s Department of Biomedical Engineering in the Cockrell School of Engineering believe the key to understanding the progression of breast cancer might lie in the tiny area just outside of a cancer cell.

Biomedical engineering professor Laura Suggs and her students are working on an in-depth study of the extracellular matrix, the perimeter outside the cell. She became interested in this part of the cell after reading literature suggesting that tumor stiffness, also known as extracellular matrix stiffness, can drive cancer cells to metastasize. According to some health experts, metastasis — the spreading of cancer cells to other parts of the body — is the cause of more than 90 percent of cancer deaths.

Today, Suggs and her students are gaining insights into the extracellular matrix that could one day help take some of the guesswork out of cancer diagnosis and treatment. Now, thanks to a recent three-year, $900,000 Cancer Prevention and Research Institute (CPRIT) grant, Suggs’ lab can accelerate the pace of its discoveries.

“What this grant is going to allow is some new techniques and systems to evolve from a bioengineering perspective to look at new targets for cancer,” Suggs said.

As part of their breast cancer research, Laura Suggs and her students have created a hydrogel system. The diagram illustrates how their system transforms normal cells into cancer cells.

Since starting the research two years ago, Suggs has collaborated with biomedical engineering graduate student Ryan Stowers and chemical engineering undergraduate Bill Han on the creation of an artificial extracellular matrix and a hydrogel-based system that allows them to mimic what happens to cells when a tumor becomes hardened. Their system relies on a hydrogel material based on seaweed-derived alginate that can be combined with calcium and gold nanoparticles, all substances that are non-toxic.

They are working on refining the system so that researchers can control the characteristics of the extracellular matrix using hydrogels that draw out what the cells are going to do. Using different levels of infrared light, the researchers are able to fine-tune the mechanical properties of the gel, and either stiffen or soften the cells.

For example, they add calcium to hydrogels to stiffen the cells. The process can be reversed using citrate, which pulls calcium out of the gel, to soften the cells. In previous experiments, the researchers have injected epithelial cells — the cells that line the mammary glands — into the hydrogels.

“What we’ve accomplished so far is characterized how much stiffening we can induce with our light-triggered system,” Stowers said. Now “the goal is to unravel the mechanisms behind how the cells are transforming from normal to malignant cancer cells.”

The hydrogel system could one day uncover ways of using the extracellular matrix to slow down or stop the spread of cancer.

“Can softening – independent of anything the drugs is doing – limit metastasis?” Suggs said.

Indeed, the ability to evaluate and control the extracellular matrix could prove tremendously helpful in cancer diagnosis and treatment.

“It’s possible that the drugs that cause the extracellular matrix to get softer are not effective because you’re adding it at the wrong time or adding it with another drug that is going to counteract that,” Suggs said.

If the softening of the extracellular matrix can limit the migration of cancer cells, “we can think about how drugs can be used in combination or at a particular time,” Suggs added. “Right now, if I have a drug that is going to be effective in treating breast cancer, I may not know when to add it.”

At the end of the three-year grant Suggs hopes to have a system in place for evaluating the effect of stiffness in a mouse model, which could in turn inform researchers in the design of clinical trials. Suggs and her team plan to begin working with cancer biologist Carla Vandenberg at Dell Pediatric Institute on mouse models sometime this year.