Physics could answer questions about breast cancer spreading to bones

IUPUI researchers hope to learn how cancer cells generate enough force to move from a tumor site through the body and then settle into bones

INDIANAPOLIS -- To fully understand why breast cancer spreads, or metastasizes, you must also consider the how.

That's what researchers in a biophysics and imaging laboratory in the School of Science at IUPUI did as they studied the mechanics of cell migration, which can possibly explain how cancer cells generate enough force to move from the primary tumor site through the body and then settle into bones, said Jing Liu, an assistant professor in the school's Department of Physics, a Purdue University program. Nearly 30 percent of breast cancer metastasizes to other organs, with bones being among the most frequent sites.

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Technology enables researchers at IUPUI to examine a single cell at a time, helping them pinpoint useful information. Photo by Getty Images

A paper with the researchers' findings was recently published in the journal Scientific Reports. Liu and Hiroki Yokota, a professor of biomedical engineering at IUPUI, are co-corresponding authors of the paper.

"From a physics point of view, all the cell migration is driven by force," Liu said. "We really want to discover the force architecture of a cell and deliver the biomechanical and biophysical explanations toward cellular activities. The major focus of our lab is developing imaging methods to physically interpret cancer biology."

Description of the following video:

[Words appear in lower-left corner: IUPUI presents]

[Video: An animated microscope slides from the right side of the screen. It is on a yellow background. Three animated cells appear to the left of the microscope in a lighter yellow triangle. They are each in a blue circle, and they are moving within their circles. Later, two of the cells disappear, and the cell closest to the microscope grows larger. Its blue circle continues to rotate.]

Jing Liu, an assistant professor in the Department of Physics, speaks in voiceover: Instead of looking at millions of cells, now technology enables us to look at a single cell. When the system is growing smaller and smaller, …

[Video: Liu is looking into a microscope.]

Liu speaks in voiceover: … the physical parameter inside the …

[Video: Liu appears on camera.]

[Words appear: Jing Liu, Assistant Professor, Department of Physics]

Liu speaks: … biology system becomes more and more useful and more and more important. 

[Video, in animation: Light blue gears rotate on a blue background. In front of the gears is a science lab table. On top of the table are beakers, test tubes and a microscope.]

[Words appear: Physical science can contribute to the]   

Liu speaks in voiceover: What the physical science can contribute to the understanding of…

[Video: An animated cell moves across the center of the screen. The cell is pink and yellow, and it is on a gray background.]

[Words appear: understanding of cancer cells.]   

Liu speaks in voiceover: … this cancer biology is that,

[Video: An animated clipboard slides from the right side of the screen. It is brown and white and is on a purple background.]

[Words appear: It will provide a clear concept.]   

Liu speaks in voiceover: … they will provide a very detailed, a very solid, fundamental concept ...

[Video: Liu appears on camera.]

Liu speaks: … that will support this phenomenon, that's been observed by other biologists.

[Video animation: A microscope slides from the right side of the screen. It is on a pink background. Three cells appear to the left of the microscope in a yellow triangle, as if coming off of the viewing plate. They are each in a blue circle and are moving within their circles.]

Liu speaks in voiceover: All of the migration we have here, of the cancer cell is …

[Video: Animated gears slide from the right of the screen. They are rotating and are gray. The gears are on a purple background.]

[Words appear: is all driven by the mechanical force that generates its motor.]

 Liu speaks in voiceover: … all driven by the mechanical force that's generated on its motor.

[Video animation: A car drives along a street. The car is blue and on a yellow background. Behind the car is a silhouette of a cityscape.]

Liu speaks in voiceover: For example, like the engine of the car -- the engine of the car…

[Video animation: A car slides from the left of the screen. The car is white and is on a green background with trees behind the car. Text appears above the car. Later, an orange background covers the right side of the screen. A tire slides from the right, at a side view. The tire is rotating. Text appears above the tire.]

[Words appear: The engine of the car generates the power that drives the wheel of the vehicle.] 

Liu speaks in voiceover: … generates the power that drives the wheel of the vehicle to move forward.

[Video: Liu appears on camera.] 

Liu speaks: So, it's the same situation for the cells to migrate.

[Video animation: The left half of the screen is blue. An cell slides in on the left side from the top of the screen. It has many colors in it and is rotating. Text appears below it. The right half of the screen is green. An animated hand appears, holding a key. The hand is turning the key in a car ignition. Text appears below it.] 

[Words appear: The cell migration is controlled by the engine of the cell]

Liu speaks in voiceover: The cell migration is controlled by the engine of the cell, …

[Video animation: Gears slide from the top of the screen. They are on a teal background. The gears are a gray color and are rotating. Text appears below them.] 

[Words appear: which is called the atp synthase,]

Liu speaks in voiceover: … which is called the atp synthase, …

 [Video animation: A tire slides down from the top of the screen, showing side view. The tire is rotating. It is on a purple background. Text is below it.]

[Words appear: and its wheel is called focal adhesion.]

Liu speaks in voiceover: … and its wheel is called focal adhesion. 

[Video animation: A car drives along a street. The car is blue and on a yellow background. Behind the car is a silhouette of a cityscape. Text is above the car.] 

[Words appear: The focal adhesion functions as the wheels of the car.]

Liu speaks in voiceover: So, this focal adhesion is functioning as the wheels of the car. 

[Video: Liu appears on camera.]

Liu speaks: By looking at the forces on this focal adhesion, …

[Video: Liu is shown in a laboratory. He is looking at a computer and typing on a keyboard. Later he is seen looking into a microscope.]

Liu speaks in voiceover: … we will be able to know how fast these cells will move. 

[Screen goes to black]

[IU trident appears]

[Words appear: IUPUI]

[Words appear: Fulfilling the promise]

[Words appear: iupui.edu]

 

[END OF TRANSCRIPT]

 

The major focus of the lab is developing imaging methods to physically interpret cancer biology.

"We are working with mathematicians and engineers to develop a mathematical model and physical model of the cell migration," Liu said.

A Forster resonance energy transfer-based tension, or FRET, sensor was used to monitor the force dynamics during cell movement. The sensor, equipped with FRET molecules, acts like a spring to measure the tiny amount of force that is generated by the cancer cell through focal adhesion and that drives the cell to move. As the cancer cell moves, the spring expands; researchers measure the force by monitoring the change of FRET interactions.

The team at IUPUI monitored the mobility of the cancer cells and found that when a cancer cell interacts with and gets very close to a bone cell, it exhibits low tensions and slow mobility, Liu said. The researchers hope this finding might lead to clues for how to control -- and eventually stop -- cell migration.

"This gives us a more precise measurement of how fast the cell is moving and where the cell will go to," Liu said. It will also provide feedback to cancer biologists, showing the impact of a drug or other treatment on the movement of the cells.

"The basic idea is to use imaging as a method to see some of the physical parameters in cancer biology,"Liu said. "Instead of only being able to look at millions of cells at time, technology has enabled us to examine a single cell. When the system is going smaller and smaller, the physical parameters inside the biological system become more and more useful and more and more important."

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