Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Massachussetts General-developed device monitors key step in development of tumor metastases

19.08.2014

A microfluidic device developed at Massachusetts General Hospital (MGH) may help study key steps in the process by which cancer cells break off from a primary tumor to invade other tissues and form metastases.

In their report published in Nature Materials, the investigators describe an stands for epithelial-mesenchymal transition, a fundamental change in cellular characteristics that has been associated with the ability of tumor cells to migrate and invade other sites in the body. Therapies that target this process may be able to slow or halt tumor metastasis.


As cells undergoing the epithelial-mesenchymal transition move from left to right through the EMT chip, those expressing mesenchymal markers (red) break away and move independently from other cells, while cells expressing epithelial markers (green) continue to move as a collective front.

Credit: BioMEMS Resource Center, Massachusetts General Hospital

"This device gives us a platform to be used in testing and comparing compounds to block or delay the epithelial-mesenchymal transition, potentially slowing the progression of cancer," says Daniel Irimia, MD, PhD, associate director of the BioMEMS Resource Center in the MGH Department of Surgery.

Normally a stage in embryonic development, EMT is important during normal wound healing and also appears to take place when epithelial cells lining bodily surfaces and cavities become malignant. Instead of adhering to each other tightly in layers, cells that have undergone EMT gain the ability to separate out, move to other parts of the body and implant themselves into the new sites. Cells that have transitioned into a mesenchymal state appear to be more resistant to cancer therapies or other measures designed to induce cell death.

The device developed at the MGH allows investigator to follow the movement of cells passing through a comb-like array of micropillars, which temporarily separates cells that are adhering to each other. To establish baseline characteristics of noncancerous cells, the investigators first studied the passage of normal epithelial cells through the array. They observed that those cells moved at the same speed as neighboring cells, reconnecting when they come into contact with each other into multicellular sheets that repeatedly break apart and reseal. Tumor cells, however, passed quickly and more directly through the device and did not interact with nearby cells.

When cells in which the process of EMT had been initiated by genetic manipulation were observed passing through the device, at first they migrated collectively. But soon after encountering the first micropillars, many cells broke away from the collective front and migrated individually for the rest of their trajectory.

Some cells appeared to undergo the opposite transition, reverting from individual migration back to collective migration. Subsequent analysis revealed that the slower moving cells that continued migrating together expressed epithelial markers, while the faster moving, independently migrating cells expressed mesenchymal markers. The individually cells migrating also appeared to be more resistant to treatment with chemotherapy drugs.

A particular advantage of the EMT chip is the ability to observe how the behavior of a population of cells changes over time. "Instead of providing a snapshot of cells or tissues at a specific moment, as traditional histology studies do, the new chip can capture the changing dynamics of individual or collective cellular migration," explains Irimia, an assistant professor of Surgery at Harvard Medical School.

"In the controlled environment of the EMT chip, these processes resemble such phase transitions as the change from solid to liquid that occurs with melting. Analogies with well studied physical processes are very useful for summarizing the complex EMT process into a few parameters. These parameters are very helpful when making comparisons between different cell types and studying the contribution of various biological processes to EMT. They are also useful when comparing different chemicals to discover new compounds to block or delay EMT"

###

Ian Wong, PhD, formerly of the BioMEMS Resource Center and now at the Brown University School of Engineering, is lead author of the Nature Materials paper. Additional co-authors are Elisabeth Wong, Sinem Park, PhD, and Mehmet Toner, PhD, BioMEMS Resource Center; and Sarah Javaid, PhD, and Daniel Haber, MD, MGH Cancer Center. The study was supported by grants from the Merck Fellowship of the Damon Runyon Cancer Research Foundation, Howard Hughes Medical Institute, and National Institutes of Health grants CA129933, EB002503, CA135601 and GM092804.

Massachusetts General Hospital, founded in 1811, is the original and largest teaching hospital of Harvard Medical School. The MGH conducts the largest hospital-based research program in the United States, with an annual research budget of more than $785 million and major research centers in HIV/AIDS, cardiovascular research, cancer, computational and integrative biology, cutaneous biology, human genetics, medical imaging, neurodegenerative disorders, regenerative medicine, reproductive biology, systems biology, transplantation biology and photomedicine.

Katie Marquedant | Eurek Alert!

Further reports about: Cancer EMT epithelial mesenchymal metastases migrating processes transition

More articles from Life Sciences:

nachricht Locusts provide insight into brain response to stimuli, senses
28.04.2015 | Washington University in St. Louis

nachricht Discovery of an unexpected function of a protein linked to neurodegenerative diseases
28.04.2015 | Institute for Research in Biomedicine (IRB Barcelona)

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Fast and Accurate 3-D Imaging Technique to Track Optically-Trapped Particles

KAIST researchers published an article on the development of a novel technique to precisely track the 3-D positions of optically-trapped particles having complicated geometry in high speed in the April 2015 issue of Optica.

Daejeon, Republic of Korea, April 23, 2015--Optical tweezers have been used as an invaluable tool for exerting micro-scale force on microscopic particles and...

Im Focus: NOAA, Tulane identify second possible specimen of 'pocket shark' ever found

Pocket sharks are among the world's rarest finds

A very small and rare species of shark is swimming its way through scientific literature. But don't worry, the chances of this inches-long vertebrate biting...

Im Focus: Drexel materials scientists putting a new spin on computing memory

Ever since computers have been small enough to be fixtures on desks and laps, their central processing has functioned something like an atomic Etch A Sketch, with electromagnetic fields pushing data bits into place to encode data.

Unfortunately, the same drawbacks and perils of the mechanical sketch board have been just as pervasive in computing: making a change often requires starting...

Im Focus: Exploding stars help to understand thunderclouds on Earth

How is lightning initiated in thunderclouds? This is difficult to answer - how do you measure electric fields inside large, dangerously charged clouds? It was discovered, more or less by coincidence, that cosmic rays provide suitable probes to measure electric fields within thunderclouds. This surprising finding is published in Physical Review Letters on April 24th. The measurements were performed with the LOFAR radio telescope located in the Netherlands.

How is lightning initiated in thunderclouds? This is difficult to answer - how do you measure electric fields inside large, dangerously charged clouds? It was...

Im Focus: On the trail of a trace gas

Max Planck researcher Buhalqem Mamtimin determines how much nitrogen oxide is released into the atmosphere from agriculturally used oases.

In order to make statements about current and future air pollution, scientists use models which simulate the Earth’s atmosphere. A lot of information such as...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

HHL Energy Conference on May 11/12, 2015: Students Discuss about Decentralized Energy

23.04.2015 | Event News

“Developing our cities, preserving our planet”: Nobel Laureates gather for the first time in Asia

23.04.2015 | Event News

HHL's Entrepreneurship Conference on FinTech

13.04.2015 | Event News

 
Latest News

Siemens opens new location for eCar Powertrain Systems Business Unit

28.04.2015 | Press release

Innovative LED high power light source with up to six wavelengths

28.04.2015 | Power and Electrical Engineering

‘Dead zones’ found in Atlantic open waters

28.04.2015 | Earth Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>