Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

A microchip for metastasis

07.02.2014
MIT researchers design a microfluidic platform to see how cancer cells invade specific organs.

Nearly 70 percent of patients with advanced breast cancer experience skeletal metastasis, in which cancer cells migrate from a primary tumor into bone — a painful development that can cause fractures and spinal compression.


A three-dimensional reconstruction of a confocal image for a bone-mimicking microenvironment (green). Endothelial cells (red), mimic blood vessels, with breast cancer cells (blue) passing through the endothelial wall, into the bone-like matrix.

Photo: Jessie Jeon

While scientists are attempting to better understand metastasis in general, not much is known about how and why certain cancers spread to specific organs, such as bone, liver, and lungs.

Now researchers from MIT, Italy, and South Korea have developed a three-dimensional microfluidic platform that mimics the spread of breast cancer cells into a bonelike environment.

The microchip — slightly larger than a dime — contains several channels in which the researchers grew endothelial cells and bone cells to mimic a blood vessel and bone side-by-side. They then injected a highly metastatic line of breast cancer cells into the fabricated blood vessel.

Twenty-four hours later, the team observed that twice as many cancer cells had made their way through the vessel wall and into the bonelike environment than had migrated into a simple collagen-gel matrix. Moreover, the cells that made it through the vessel lining and into the bonelike setting formed microclusters of up to 60 cancer cells by the experiment’s fifth day.

“You can see how rapidly they are growing,” says Jessie Jeon, a graduate student in mechanical engineering. “We only waited until day five, but if we had gone longer, [the size of the clusters] would have been overwhelming.”

The team also identified two molecules that appear to encourage cancer cells to metastasize: CXCL5, a protein ligand secreted by bone cells, and CXCR2, a receptor protein on cancer cells that binds to the ligand. The preliminary results suggest that these molecules may be potential targets to reduce the spread of cancer.

Jeon says the experiments demonstrate that the microchip may be used in the future to test drugs that might stem metastasis, and also as a platform for studying cancer’s spread to other organs.

She and her colleagues, including Roger Kamm, the Cecil and Ida Green Distinguished Professor of Mechanical and Biological Engineering at MIT, have outlined the results of their experiments in the journal Biomaterials.

“Currently, we don't understand why certain cancers preferentially metastasize to specific organs,” Kamm says. “An example is that breast cancer will form metastatic tumors in bone, but not, for example, muscle. Why is this, and what factors determine it? We can use our model system both to understand this selectivity, and also to screen for drugs that might prevent it.”

Through a wall and into bone

The process by which cancer cells form secondary tumors requires the cells to first survive a journey through the circulatory system. These migrating cells attach to a blood vessel’s inner lining, and ultimately squeeze through to the surrounding tissue — a process called extravasation, which Kamm’s research group modeled last fall using a novel microfluidic platform.

Now the group is looking to the next step in metastasis: the stage at which a cancer cell invades a specific organ. In particular, the researchers designed a microchip in which they could observe interactions between specific cancer cells and a receptive, organlike environment. They chose to work first with osteo-differentiated cells, as bone is a major target of metastasizing breast cancer cells.

The group collected marrow-derived stem cells from patients undergoing hip surgery, and allowed the cells to naturally differentiate into bone cells. They also obtained commercially available endothelial cells, and lined one channel in the microchip with endothelial cells to mimic a blood vessel wall. They filled another channel with differentiated bone cells to form a bonelike matrix, and finally injected human breast cancer cells into the channel containing endothelial cells.

Jeon and her colleagues captured images of the metastatic process: Cancer cells pushed through the vessel wall, spread into the bonelike environment, and clustered deep in the bone matrix to form tiny tumors.

In particular, they found that twice as many cancer cells spread to the bonelike environment as to a standard collagen matrix; these also spread deeper into the bone matrix, forming microclusters of up to 60 cells after five days.

To see what molecular signals might explain the difference in metastatic rate, the team focused on CXCL5 and CXCR2. While these two proteins are known to have a role in metastasis, it’s not clear whether they promote it in specific organs.

The researchers incubated cancer cells with an antibody that blocked CXCR2, and found that these cells were less able to break through the blood vessel lining. They also tried injecting CXCL5 into a collagen-gel matrix without bone cells, and found that the ligand-seeded environment encouraged breast cancer cells to invade. The results suggest these two proteins may be targets for preventing or mitigating cancer metastasis not just in bone, but in other organs as well.

“The beauty of this system lies in its simplicity and elegance,” says Muhammad Zaman, an associate professor of biological engineering at Boston University who was not involved in the research. “I believe that this microfluidic system will be easy to scale to study processes that are important yet have been too difficult to quantify. Overall, I think this is a major breakthrough to understand complex processes, underscore the importance of mechanics and identify novel pathways for treatment.”

The team plans to explore cancer metastasis in other organs, such as muscle — an organ in which cancer cells do not easily spread.

“There are some organs known to be more or less metastatic, and if we can add two different organ types, we can see what kind of differences there are,” Jeon says.

Kamm adds that in the future, such a platform may be used in personalized medicine to determine the best cancer therapy for a given patient.

“One might envision using cells from the cancer patient to produce models of different organs, then using these models to determine the optimal therapy from a variety of available drugs,” Kamm says.

This research was supported by the National Cancer Institute and the Italian Ministry of Health.

Kimberly Allen | EurekAlert!
Further information:
http://www.mit.edu

More articles from Life Sciences:

nachricht Multi-institutional collaboration uncovers how molecular machines assemble
02.12.2016 | Salk Institute

nachricht Fertilized egg cells trigger and monitor loss of sperm’s epigenetic memory
02.12.2016 | IMBA - Institut für Molekulare Biotechnologie der Österreichischen Akademie der Wissenschaften GmbH

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Novel silicon etching technique crafts 3-D gradient refractive index micro-optics

A multi-institutional research collaboration has created a novel approach for fabricating three-dimensional micro-optics through the shape-defined formation of porous silicon (PSi), with broad impacts in integrated optoelectronics, imaging, and photovoltaics.

Working with colleagues at Stanford and The Dow Chemical Company, researchers at the University of Illinois at Urbana-Champaign fabricated 3-D birefringent...

Im Focus: Quantum Particles Form Droplets

In experiments with magnetic atoms conducted at extremely low temperatures, scientists have demonstrated a unique phase of matter: The atoms form a new type of quantum liquid or quantum droplet state. These so called quantum droplets may preserve their form in absence of external confinement because of quantum effects. The joint team of experimental physicists from Innsbruck and theoretical physicists from Hannover report on their findings in the journal Physical Review X.

“Our Quantum droplets are in the gas phase but they still drop like a rock,” explains experimental physicist Francesca Ferlaino when talking about the...

Im Focus: MADMAX: Max Planck Institute for Physics takes up axion research

The Max Planck Institute for Physics (MPP) is opening up a new research field. A workshop from November 21 - 22, 2016 will mark the start of activities for an innovative axion experiment. Axions are still only purely hypothetical particles. Their detection could solve two fundamental problems in particle physics: What dark matter consists of and why it has not yet been possible to directly observe a CP violation for the strong interaction.

The “MADMAX” project is the MPP’s commitment to axion research. Axions are so far only a theoretical prediction and are difficult to detect: on the one hand,...

Im Focus: Molecules change shape when wet

Broadband rotational spectroscopy unravels structural reshaping of isolated molecules in the gas phase to accommodate water

In two recent publications in the Journal of Chemical Physics and in the Journal of Physical Chemistry Letters, researchers around Melanie Schnell from the Max...

Im Focus: Fraunhofer ISE Develops Highly Compact, High Frequency DC/DC Converter for Aviation

The efficiency of power electronic systems is not solely dependent on electrical efficiency but also on weight, for example, in mobile systems. When the weight of relevant components and devices in airplanes, for instance, is reduced, fuel savings can be achieved and correspondingly greenhouse gas emissions decreased. New materials and components based on gallium nitride (GaN) can help to reduce weight and increase the efficiency. With these new materials, power electronic switches can be operated at higher switching frequency, resulting in higher power density and lower material costs.

Researchers at the Fraunhofer Institute for Solar Energy Systems ISE together with partners have investigated how these materials can be used to make power...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

ICTM Conference 2017: Production technology for turbomachine manufacturing of the future

16.11.2016 | Event News

Innovation Day Laser Technology – Laser Additive Manufacturing

01.11.2016 | Event News

#IC2S2: When Social Science meets Computer Science - GESIS will host the IC2S2 conference 2017

14.10.2016 | Event News

 
Latest News

UTSA study describes new minimally invasive device to treat cancer and other illnesses

02.12.2016 | Medical Engineering

Plasma-zapping process could yield trans fat-free soybean oil product

02.12.2016 | Agricultural and Forestry Science

What do Netflix, Google and planetary systems have in common?

02.12.2016 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>