Mechanobiology could explain mystery of relapses in cancer patients

The recurrence of cancer has been one of the greatest mysteries plaguing the medical research field. After weeks, or even years of being declared cancer-free, a patient can see their cancer return stronger than it was before. It is every cancer survivor’s greatest fear.

Ning Wang, a professor in the Department of Mechanical Science and Engineering at the University of Illinois at Urbana-Champaign, has been applying mechanical engineering to biological questions for almost 30 years. Recently his research has turned its focus to the disease that is estimated to kill about 500,000 people each year, and specifically, on the mystery of its recurrence.

Wang’s most recent work tries to explain why patients experience relapses in cancer. It is unclear why or how cancer relapses. Experiments have shown that between a quarter of a million and a million typical cancerous cells are required to regenerate a tumor, but there are not that many cancer cells in the patient when they are declared to be in remission.

Research has recently surfaced that not all cancer cells are the same. Most cancer cells do not have an unlimited capacity to multiply and create tumors. For the majority of cancer cells, if they somehow escape the parent tumor to other parts of the body, they die there, unable to reproduce. However, there are a small percentage of cancer cells that can replicate indefinitely, and it is believed that they are responsible for tumor growth. They are called cancer stem cells, tumor founding cells, or tumor repopulating cells. Where it takes hundreds of thousands of normal cancer cells to regenerate a tumor, it only takes ten tumor repopulating cells to do so.

Wang’s research has found a way to identify these cells using mechanics.

“There was a lot of controversy and debate about it. People were using everything they could to try and identify them,” Wang said, “but their results couldn’t be replicated by other groups because different groups used different mechanical environments. So we basically unified them and thought that if we controlled the mechanical environment, we could actually separate the tumor creating cells.”

By realizing the importance of mechanical forces on cells, Wang said his group discovered what other research groups could not.

These cells have been found extremely resistant to chemotherapy, and even to cancer-treating drugs that are very effective against normal cancer cells.

“So this raises the question why are they like this?” Wang said. “And the answer is that we don’t know. That’s the problem we’re working on.”

Wang has applied his mechanical engineering knowledge to many other biological mysteries. For example, how do mechanical forces on the cell translate to different cellular behaviors? The process is called mechanotransduction: mechanical forces can go through specific molecules and proteins in the cell membrane, cross the membrane, and transduce signals to the interior of the cell. Wang postulated that the initial mechanical energy was transmitted through filaments within the cell all the way to the nucleus, and could therefore alter genetic expression with unpredictable results.

“You can’t just relate one force and one gene,” Wang said, “because when you apply one force, you cannot say just one gene gets turned on and turned off. It’s not that simple. It could be a few, or a group of genes.”

Another of his recent significant breakthroughs was discovering that using a soft substrate to culture stem cells would keep them in their pluripotent state. Previously, researchers had used expensive chemicals called growth factors to keep the stem cells from spontaneously differentiating. The more inexpensive solution of using a soft substrate to keep them in their dedifferentiated state is a major step forward for stem cell research.

“What kind of impact is our research going to have on the rest of the nation or the world?” Wang said. “Can we make a big impact? Can we make others follow our work? That’s how science progresses. And I think our department is working in the right direction in biomechanics. We focus our expertise on certain areas to do pioneering work, work that people can follow. That’s really the most important.”
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Contact: Ning Wang, Department of Mechanical Science and Engineering, 217/265-0913.

Writer: Meredith Staub

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