Corporate Banner
Satellite Banner
Automation & Microfluidics
Scientific Community
 
Become a Member | Sign in
Home>News>This Article
  News
Return

Watching Tumors Burst Through a Blood Vessel

Published: Tuesday, September 24, 2013
Last Updated: Tuesday, September 24, 2013
Bookmark and Share
A microfluidic platform provides a high-resolution view of a crucial step in cancer metastasis.

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.”

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.

Muhammad Zaman, an associate professor of biomedical engineering at Boston University, says that tumor intravasation is a major step in metastasis that has been poorly understood due to a lack of robust and scalable tools.

“The work by Kamm and co-workers has provided a highly innovative, controlled and robust system to analyze this key process in exquisite detail,” says Zaman, who was not involved in this research. “This significantly reduces costs with animal models, addresses issues seen in typical in-vitro cultures and, above all, provides quantitative detail.”

“The impact of this work will be profound,” Zaman adds. “I anticipate that both researchers and [pharmaceutical companies] will use this tool to characterize and analyze complex processes of tumor extravasation.”


Further Information

Join For Free

Access to this exclusive content is for Technology Networks Premium members only.

Join Technology Networks Premium for free access to:

  • Exclusive articles
  • Presentations from international conferences
  • Over 3,300+ scientific posters on ePosters
  • More than 4,900+ scientific videos on LabTube
  • 35 community eNewsletters


Sign In



Forgotten your details? Click Here
If you are not a member you can join here

*Please note: By logging into TechnologyNetworks.com you agree to accept the use of cookies. To find out more about the cookies we use and how to delete them, see our privacy policy.

Related Content

New Device can Study Electric Field Cancer Therapy
Microfluidic device allows study of electric field cancer therapy through low-intensity fields, preventing malignant cells spreading.
Friday, July 08, 2016
Tough New Hydrogel Hybrid Doesn’t Dry Out
Water-based material could be used to make artificial skin, longer-lasting contact lenses.
Friday, July 01, 2016
Organ-on-a-Chip
In a step toward personalized drug testing, researchers coax human stem cells to form complex tissues.
Friday, January 08, 2016
Study Reveals Shared Behavior of Microbes And Electrons
Bacteria streaming through a lattice behave like electrons in a magnetic material.
Wednesday, January 06, 2016
Study Reveals Shared Behavior of Microbes and Electrons
Bacteria streaming through a lattice behave like electrons in a magnetic material.
Wednesday, January 06, 2016
Tracing a Cellular Family Tree
New technique allows tracking of gene expression over generations of cells as they specialize.
Wednesday, January 06, 2016
New Device Uses Carbon Nanotubes to Snag Molecules
Nanotube “forest” in a microfluidic channel may help detect rare proteins and viruses.
Tuesday, December 22, 2015
Scaling Up Synthetic-Biology Innovation
MIT professor’s startup makes synthesizing genes many times more cost effective.
Monday, December 14, 2015
Capturing Cell Growth in 3-D
Spinout’s microfluidics device better models how cancer and other cells interact in the body.
Monday, August 17, 2015
Real-Time Data for Cancer Therapy
Biochemical sensor implanted at initial biopsy could allow doctors to better monitor and adjust cancer treatments.
Thursday, August 06, 2015
Freshly Squeezed Vaccines
Microfluidic cell-squeezing device opens new possibilities for cell-based vaccines.
Saturday, May 23, 2015
Faster, Smaller, More Informative
Device can measure the distribution of tiny particles as they flow through a microfluidic channel.
Thursday, May 14, 2015
Using Sound Waves To Detect Rare Cancer Cells
Acoustic device can rapidly isolate circulating tumor cells from patient blood samples.
Tuesday, April 07, 2015
Mechanically Stimulating Stem Cells
MIT biological engineering graduate student Frances Liu is studying ways to alter mechanical properties of cell environments to produce desired chemical outputs.
Tuesday, March 24, 2015
New Way To Model Sickle Cell Behavior
Microfluidic device allows researchers to predict behavior of patients’ blood cells.
Wednesday, January 21, 2015
Scientific News
Diagnostic Thread - Weaving the Future?
Researchers have created diagnostic threads that could pave the way for next-gen implantable and wearable diagnostics.
R&D Agreement for Development of CtDNA Diagnostics
SeraCare and NIST partner for development of ctDNA diagnostic assay reference materials.
Adipose Analysis on Microfluidic Chips
Scientists have developed a microfluidic chip the works with minute liquid quantities to grow and study cells.
New Device can Study Electric Field Cancer Therapy
Microfluidic device allows study of electric field cancer therapy through low-intensity fields, preventing malignant cells spreading.
DNA Production Facility Begins Operation
Scientists mark the opening of the UK's first fully automated DNA construction and modification facility.
A “Micro Winery” That Makes Wine Continuously
An American professor, working in collaboration with EPFL, is developing a miniature device for producing wine non-stop and testing different fermentation processes.
Testing for Malaria or Cancer at Home
Chemist develops tech to save lives in rural Africa.
Tough New Hydrogel Hybrid Doesn’t Dry Out
Water-based material could be used to make artificial skin, longer-lasting contact lenses.
Lasers Carve the Path to Tissue Engineering
A new technique, developed at EPFL, combines microfluidics and lasers to guide cells in 3D space, overcoming major limitations to tissue engineering.
A Future Tool for Medicine, Food Safety
A new type of electronic sensor that might be used to quickly detect and classify bacteria for medical diagnostics and food safety has passed a key hurdle by distinguishing between dead and living bacteria cells.
Scroll Up
Scroll Down
SELECTBIO

SELECTBIO Market Reports
Go to LabTube
Go to eposters
 
Access to the latest scientific news
Exclusive articles
Upload and share your posters on ePosters
Latest presentations and webinars
View a library of 1,800+ scientific and medical posters
3,300+ scientific and medical posters
A library of 2,500+ scientific videos on LabTube
4,900+ scientific videos
Close
Premium CrownJOIN TECHNOLOGY NETWORKS PREMIUM FOR FREE!