Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Microfluidic platform gives a clear look at a crucial step in cancer metastasis

23.09.2013
Cancer cells metastasize in several stages -- first by invading surrounding tissue, then by infiltrating and spreading via the circulatory system. Some circulating cells work their way out of the vascular network, eventually forming a secondary tumor.

While the initial process by which cancer cells enter the bloodstream -- called intravasation -- is well characterized, how cells escape blood vessels to permeate other tissues and organs is less clear. This process, called extravasation, is a crucial step in cancer metastasis.

Now researchers at MIT have developed a microfluidic device that mimics the flow of cancer cells through a system of blood vessels. Using high-resolution time-lapse imaging, the researchers captured the moments as a cancer cell squeezes its way through a blood vessel wall into the surrounding extracellular matrix. The process is "highly dynamic," as they write in a paper published in the journal Integrative Biology; a better understanding of it may help scientists identify therapies to prevent metastasis.

"Now that we have a model for extravasation, you can think about using it as a screen for drugs that could prevent it," says Roger Kamm, the Cecil and Ida Green Distinguished Professor of Biology and Mechanical Engineering at MIT. "We could take circulating tumor cells from a patient and subject those cells to a handful of factors or drugs. That's ultimately what we'd like to do, but in the process we're learning a lot as we go along."

Kamm's co-authors on the paper include graduate students Michelle Chen, Jordan Whisler and Jessie Jeon.

Seeding blood vessels

As tumor cells make their way through the circulatory system, some "arrest," or pause at a particular location, adhering to a blood vessel's wall -- the first stage of extravasation. Scientists have thought that this cell arrest occurs in one of two ways: A cell may send out sticky projections that grab onto the vessel lining, or it may be too big to pass through, literally becoming trapped within the vessel.

To investigate which possibility is more likely, the researchers grew a network of tiny blood vessels from a solution of human umbilical-cord endothelial cells. They injected a solution containing vascular cells into a small microfluidic device containing a reservoir of hydrogel, along with growth factors normally present in the developing circulatory system. Within days, an intricate system of microvessels took shape, with each about one millimeter long and 10 to 100 microns in diameter -- dimensions similar to the body's small capillaries.

The group then pumped tumor cells through the vascular network, using a line of breast cancer cells known to be particularly invasive. Using high-resolution confocal microscopy, the team watched as tumor cells flowed through the miniature circulatory system. They observed that the majority of cells that arrested along a vessel did so due to entrapment -- that is, they simply became stuck.

A tumor cell finds a way out

With time-lapse images, the researchers took a closer look at the progression of events following cell arrest. Once a tumor cell becomes trapped, they observed that it sends out long, thin filaments that push against a vessel wall, eventually creating a small hole in the endothelial lining. More and more of the cell squeezes through as the holes give way, and eventually, even the cell's nucleus -- thought to be a relatively rigid, nondeformable structure -- is able to escape.

To their surprise, the researchers found that the nucleus made it through the vessel wall earlier and more quickly than they anticipated, squeezing through in about 15 minutes -- "a tiny chunk of the time it takes for this entire cell to extravasate," Chen notes.

Interestingly, Chen points out, once a tumor cell has completely exited a blood vessel, the endothelium appears to heal itself, closing the gaps that the cell initially created. "That suggests that the endothelial barrier has some kind of active role in repairing itself after this invasion by the tumor cell," Chen says.

In addition to observing the extravasation of single tumor cells, the group also looked at the behavior of cell clusters -- two or more cancer cells that accumulate in a blood vessel. From their observations, the researchers found that almost 70 percent of cell clusters broke through a blood barrier, compared with less than 10 percent of single cells.

But some cells that make it out of the circulatory system may still fail to metastasize. To see whether a cell's ability to extravasate correlates with its metastatic potential, the group compared the efficiency of extravasation of different cancer cell lines. The lines included breast cancer cells, cells from fibrosarcoma (a cancer of the connective tissue), and a line of nonmetastatic cancer cells.

Sure enough, the team observed that the most metastatic cells (fibrosarcoma cells) were also the most likely to extravasate, compared with breast cancer and nonmetastatic cells -- a finding suggesting that targeting drugs to prevent extravasation may slow cancer metastasis.

Going forward, the group is looking into how likely a given cancer cell is to proliferate and aggregate with others once it has exited into the surrounding tissue. The researchers are modeling various tissues within the microfluidic platform, including bone, to study how cancer cells form the beginnings of a secondary tumor.

"Although this platform isn't an in-vivo platform and obviously can't capture all the aspects that happen in vivo, we've come a lot closer to creating an in-vitro platform that's even more physiologically relevant, high-resolution and high-throughput than a lot of previous platforms," Chen says.

Written by Jennifer Chu, MIT News Office

Andrew Carleen | EurekAlert!
Further information:
http://www.mit.edu

More articles from Life Sciences:

nachricht What the world's tiniest 'monster truck' reveals
23.08.2017 | American Chemical Society

nachricht Treating arthritis with algae
23.08.2017 | Empa - Eidgenössische Materialprüfungs- und Forschungsanstalt

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Fizzy soda water could be key to clean manufacture of flat wonder material: Graphene

Whether you call it effervescent, fizzy, or sparkling, carbonated water is making a comeback as a beverage. Aside from quenching thirst, researchers at the University of Illinois at Urbana-Champaign have discovered a new use for these "bubbly" concoctions that will have major impact on the manufacturer of the world's thinnest, flattest, and one most useful materials -- graphene.

As graphene's popularity grows as an advanced "wonder" material, the speed and quality at which it can be manufactured will be paramount. With that in mind,...

Im Focus: Exotic quantum states made from light: Physicists create optical “wells” for a super-photon

Physicists at the University of Bonn have managed to create optical hollows and more complex patterns into which the light of a Bose-Einstein condensate flows. The creation of such highly low-loss structures for light is a prerequisite for complex light circuits, such as for quantum information processing for a new generation of computers. The researchers are now presenting their results in the journal Nature Photonics.

Light particles (photons) occur as tiny, indivisible portions. Many thousands of these light portions can be merged to form a single super-photon if they are...

Im Focus: Circular RNA linked to brain function

For the first time, scientists have shown that circular RNA is linked to brain function. When a RNA molecule called Cdr1as was deleted from the genome of mice, the animals had problems filtering out unnecessary information – like patients suffering from neuropsychiatric disorders.

While hundreds of circular RNAs (circRNAs) are abundant in mammalian brains, one big question has remained unanswered: What are they actually good for? In the...

Im Focus: RAVAN CubeSat measures Earth's outgoing energy

An experimental small satellite has successfully collected and delivered data on a key measurement for predicting changes in Earth's climate.

The Radiometer Assessment using Vertically Aligned Nanotubes (RAVAN) CubeSat was launched into low-Earth orbit on Nov. 11, 2016, in order to test new...

Im Focus: Scientists shine new light on the “other high temperature superconductor”

A study led by scientists of the Max Planck Institute for the Structure and Dynamics of Matter (MPSD) at the Center for Free-Electron Laser Science in Hamburg presents evidence of the coexistence of superconductivity and “charge-density-waves” in compounds of the poorly-studied family of bismuthates. This observation opens up new perspectives for a deeper understanding of the phenomenon of high-temperature superconductivity, a topic which is at the core of condensed matter research since more than 30 years. The paper by Nicoletti et al has been published in the PNAS.

Since the beginning of the 20th century, superconductivity had been observed in some metals at temperatures only a few degrees above the absolute zero (minus...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Call for Papers – ICNFT 2018, 5th International Conference on New Forming Technology

16.08.2017 | Event News

Sustainability is the business model of tomorrow

04.08.2017 | Event News

Clash of Realities 2017: Registration now open. International Conference at TH Köln

26.07.2017 | Event News

 
Latest News

What the world's tiniest 'monster truck' reveals

23.08.2017 | Life Sciences

Treating arthritis with algae

23.08.2017 | Life Sciences

Witnessing turbulent motion in the atmosphere of a distant star

23.08.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>