A new 3-D tumor modeling technology could drastically change the way cancer is treated. Diskoid In Geometrically Micropatterned Extracellular matrix (DIGME) is a tissue-patterning solution that uses a low-cost device to control the shape of tumors — as well as the directionality and rigidity of their surrounding matrix — to stop cancer cells from spreading.
Bo Sun, an assistant professor of physics in Oregon State’s College of Science, says DIGME will help doctors test their own cancer treatments and create new ones. And it could even improve the efficiency of early cancer detection.
“Right now, cancer detection is relying on techniques that were developed decades ago,” Sun says. “I think tumor modeling is going to show us the new things we should look at. There may be a different set of metrics that make the accuracy and sensitivity of early detection much better.”
Sun’s device can facilitate development of new cancer treatments by better mimicking the physiological condition of tumors. Oregon State University has filed for a patent and is looking for potential licensees and research collaborators to further develop the technique.
Understanding how cancer cells spread
In order for a cancer cell to dissociate from the main tumor and spread — also known as metastasis — it must dig a hole through the extracellular matrix (ECM). The ECM is the area that surrounds a tumor, which is made up of connective tissues like collagen. It can act as a barrier to keep tumor cells in or out, depending on its porousness.
For example, an ECM that is very porous provides a soft environment for cancer cells to easily squeeze through and enter other areas of the body. An ECM that is very rigid, on the other hand, provides a barricade that is very difficult for a cancer cell to dig into. However, a rigid ECM also promotes tumor growth; therefore the relationship between ECM and cancer is anything but simple. This relationship is one of the central problems of cancer research.
Modeling tumors
Sun’s team worked with standard cancer cell lines in the lab. To shape a tumor, a micro-fabricated stamp is used to create a mold made of collagen. Tumor cells are then suspended in a collagen solution and poured into the mold. The liquid collagen turns into a gel and links to the mold. The device can precisely control the location and rotation of the stamp, creating an exact shape.
Different tumor shapes equal different clinical outcomes for patients, Sun explains. If a tumor has very high curvature corners, these sharp corners are more likely to become cancer stem cells, which are very invasive and lead to metastasis.
Changing directions
Directionality is an equally important factor. The ECM — which is covered in polymer fibers — can be rotated with the help of DIGME technology. When the ECM is polarized — or given positive and negative charges — the orientation of those fibers can be rotated circularly, preventing additional cancer cells from disconnecting and spreading throughout the body. Controlling the shape and directionality allows DIGME to create challenging environments for cancer cells, testing their adaptability and understanding how they respond to treatments in complex physiological conditions.
“A tumor — no matter where it starts — is going to experience many different environments when it metastasizes into many parts of the body,” Sun says. “If a cell has no way to adapt to this new environment, it is going to stop there and won’t be able to spread.”
Sun’s research began with the goal of determining how tumors migrate and communicate with one another. Two-and-a-half years later, DIGME has the potential to help save lives.
For licensing information, please contact Jianbo Hu at jianbo.hu@oregonstate.edu or 541-737-2366.
This figure shows a breast cancer cell.
(A) DIGME consists of a diskoid – a tumor cell aggregate whose shape is tightly controlled. The example shown in A is a hexagonal diskoid of monolayer thickness. Typical diskoid thickness can range from one to five cell layers. (B) A triangle diskoid of MDA-MD-231 cells (green) in collagen matrix (labeled with fluorescent particles, blue). Top: top view. Bottom: side view. (C) A MDA-MD-231 diskoid (green) surrounded by two layers of collagen matrix with different concentrations (1.5 mg/ml, red and 3 mg/ml, blue). Top inset: the diskoid invasion into the surrounding ECM after five days. Bottom inset: confocal reflection imaging showing distinct fiber microstructures across the interface of two collagen layers. (D) A MDA-MB-231 ring diskoid with its sounding ECM circularly polarized. The configuration mimics the ductal carcinoma in vivo. Scale bars: 200 μm.
s is a fourth-year PhD student working with Prof. Janet Tate. Her research involves the design, synthesis, and characterization of thin film semiconductors for the improvement of renewable energy applications such as solar cells, thermoelectrics (materials which can convert heat to usable energy), or piezoelectrics (materials which can convert a mechanical stress or push to a usable energy). These semiconductors are stabilized in higher energy states than they would normally be found in through alloying and appropriate temperature control to improve their properties and make them more suitable for devices. She is particularly interested in studying the microstructure (e.g. size, composition, structure, and orientation of crystals on a very small scale) of these materials by electron microscopy and learning how changes to that microstructure explain changes to properties on a much larger scale. This fellowship will allow her to study these materials and similar systems in greater detail at the microscopy facility at the National Renewable Energy Lab in Golden, Colorado and to explain anomalous property behaviors which, if they can be controlled, could greatly increase device efficiency.
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