Any good strategist knows that an accurate map can win a battle. If your enemy is cancer, a chaotic and elusive foe that changes its environment, finding a new dimension to examine a tumor can make all the difference when developing treatments.
Like all scientists and doctors looking for ways to defeat cancer, Weimin Li wants to better understand how cancerous tumors grow and adapt. His innovative technology using 3-D tissue culture “scaffolds” delivers a far more relevant environment to research the deadly disease.
It’s a fight that Li has fought on many fronts. He spent seven years practicing oncology in China and witnessed the inconsistency of cancer treatments. “It was hard. So many patients were dying,” he says.
He was inspired to begin researching new methods of treating cancer, earning medical molecular genetics and biochemistry degrees in Scotland and Switzerland before moving to Wisconsin and then Washington State University’s Spokane campus. Along the way, Li found that the tools used by cancer researchers to model tumors were also inconsistent, often with inconclusive results.
“I realized the importance of using proper disease-modeling systems to study the mechanisms of cancer progression,” says Li. “Biologically and clinically relevant research tools can help us understand fundamental questions of cancer and develop more effective therapeutics to treat human cancer.”
Now an assistant professor in the WSU Elson S. Floyd College of Medicine, Li says that many anticancer drugs fail in clinical trials in part because they’re studied and tested in inappropriate tissue cultures or animal models.
The traditional petri dish method sets up tissue cultures in 2-D plastic systems, an artificial model that can’t represent the complex tissue environment, nor show how cells spatially interact at all levels. By creating a 3-D tissue-like scaffold, tumors can form in ways that allow scientists to screen drugs in a setting that’s a lot closer to how native cancer cells grow and invade normal human bodies.
When cancer cells are in human tissues, they interact with other cells and their environment in every direction, secrete enzymes that help the cancer to survive and spread, and even change the environment within the tissue. That can’t be truly replicated in only two dimensions.
The concept of 3-D scaffolds to grow tissue cultures is not a new one, but other 3-D culture models mostly use plastic or synthetic polymers, or they use a single component of the extracellular matrix (ECM) of disease-irrelevant animal tissues. Since tumors interact with their environment in order to survive and grow, a scaffold made from synthetic or nontissue-specific materials won’t necessarily show researchers how tumors will express biomarkers and react to drugs as they would in patients.
To overcome that problem, Li and his team built scaffolds from the ECM of normal, native tissues that preserve the tissue’s properties and match the type of cancer they want to study.
For example, they use breast tissue scaffolds for growing tumors from breast cancer cells. As tumors grow in that 3-D space, Li says the tissue matrix scaffold (TMS) creates a far more accurate replica. That optimizes research and drug development, in part because cancer cells will naturally show how they behave and resist drugs.
“There are complex interactions between cancer cells and other cells within tumors,” says Li. “We can isolate the cells and model tumor development in a way that recapitulates native conditions.”
Li’s innovation has won national awards for its novelty in modeling tissues for drug screening, but the TMS technology his team developed could have even more uses.
“One potential outcome is tissue regeneration. Another is personalized medical treatment,” he says.
For now, Li and his team, including postdoctoral colleague Girdhari Rijal, are keeping their research focused on cancer modeling and treatment. He hopes to commercialize the technology, so it can help doctors and other medical researchers to find new strategies in the ongoing fight against cancer.
NORMAL VS. TUMOROUS EXTRACELLULAR MATRICES
(Click to enlarge)
For now, Li and his team, including postdoctoral colleague Girdhari Rijal, are keeping their research focused on cancer modeling and treatment. He hopes to commercialize the technology, so it can help doctors and other medical researchers to find new strategies in the ongoing fight against cancer.