Corporate Banner
Satellite Banner
Biomolecular Screening
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
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 2,400+ scientific posters on ePosters
  • More than 3,700+ 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

Bacterial Computing
The “friendly” bacteria inside our digestive systems are being given an upgrade, which may one day allow them to be programmed to detect and ultimately treat diseases such as colon cancer and immune disorders.
Monday, July 13, 2015
Researchers Identify New Target For Anti-Malaria Drugs
Manipulating the permeability of a type of vacuole could help defeat malarial parasites.
Thursday, May 14, 2015
New Way To Turn Genes On
Technique allows rapid, large-scale studies of gene function.
Thursday, December 11, 2014
Microscopic “Walkers” Find Their Way Across Cell Surfaces
Technology could provide a way to deliver probes or drugs to cell structures without outside guidance.
Thursday, October 23, 2014
Stress-Induced Hormone Primes Brain for PTSD
MIT study finds that ghrelin, produced during stressful situations, primes the brain for post-traumatic stress disorder.
Wednesday, October 16, 2013
New Approach to Global Health Challenges
MIT’s Institute for Medical Engineering and Science brings many tools to the quest for new disease treatments and diagnostic devices.
Friday, September 27, 2013
Microfluidic Platform Gives a Clear Look at a Crucial Step in Cancer Metastasis
A microfluidic platform provides a high-resolution view of a crucial step in cancer metastasis.
Friday, September 27, 2013
Device Finds Stray Cancer Cells in Patients’ Blood
A microfluidic device that captures circulating tumor cells could give doctors a noninvasive way to diagnose and track cancers.
Wednesday, April 10, 2013
Researchers Reverse Fragile X Syndrome Symptoms in Adult Mice
Picower Institute neuroscientists use single dose of experimental drug; could prove promising for treatment of autism symptoms.
Tuesday, March 26, 2013
Chemists Find Help from Nature in Fighting Cancer
Study of several dozen compounds based on a fungal chemical shows potent anti-tumor activity.
Thursday, February 28, 2013
Bringing a New Perspective to Infectious Disease
Enlisted in the fight against HIV, MIT engineers and scientists contribute new technology, materials and computational studies.
Thursday, February 07, 2013
A Safer Way to Vaccinate
Polymer film that gradually releases DNA coding for viral proteins could offer a better alternative to traditional vaccines.
Monday, January 28, 2013
New Technology May Enable Earlier Cancer Diagnosis
Nanoparticles amplify tumor signals, making them much easier to detect in the urine.
Friday, December 21, 2012
Oscillating Microscopic Beads Could be Key to Biolab on a Chip
MIT team finds way to manipulate and measure magnetic particles without contact, potentially enabling multiple medical tests on a tiny device.
Tuesday, September 25, 2012
MIT Invents 'Lab-on-a-chip' to Automate Whole-animal Genetic and Drug Screens
Genetic studies on whole animals can now be done dramatically faster using a new microchip developed by engineers at MIT.
Wednesday, August 22, 2007
Scientific News
New Tool Uses 'Drug Spillover' to Match Cancer Patients with Treatments
Researchers have developed a new tool that improves the ability to match drugs to disease: the Kinase Addiction Ranker (KAR) predicts what genetics are truly driving the cancer in any population of cells and chooses the best "kinase inhibitor" to silence these dangerous genetic causes of disease.
HIV Susceptibility Linked to Little-Understood Immune Cell Class
High levels of diversity among immune cells called natural killer cells may strongly predispose people to infection by HIV, and may be driven by prior viral exposures, according to a new study.
Sweet Revenge Against Superbugs
A special type of synthetic sugar could be the latest weapon in the fight against superbugs.
Access Denied: Leukemia Thwarted by Cutting Off Link to Environmental Support
A new study reveals a protein’s critical – and previously unknown -- role in the development and progression of acute myeloid leukemia (AML), a fast-growing and extremely difficult-to-treat blood cancer.
Long-sought Discovery Fills in Missing Details of Cell 'Switchboard'
A biomedical breakthrough reveals never-before-seen details of the human body’s cellular switchboard that regulates sensory and hormonal responses.
Tracking Breast Cancer Before it Grows
A team of scientists led by University of Saskatchewan researcher Saroj Kumar is using cutting-edge Canadian Light Source techniques to screen and treat breast cancer at its earliest changes.
Zebrafish Reveal Drugs that may Improve Bone Marrow Transplant
Compounds boost stem cell engraftment; could allow more matches for patients with cancer and blood diseases.
DNA Damage Seen in Patients Undergoing CT Scanning
Along with the burgeoning use of advanced medical imaging tests over the past decade have come rising public health concerns about possible links between low-dose radiation and cancer.
The Light of Fireflies for Medical Diagnostics
EPFL scientists have exploited the light of fireflies in a new method that detects biological molecules without the need for complex devices and high costs.
Vital Protein in Healthy Fertilization Process Identified
Researchers at the National Institutes of Health have discovered a protein that plays a vital role in healthy egg-sperm union in mice.
SELECTBIO

Skyscraper Banner
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
2,400+ scientific and medical posters
A library of 2,500+ scientific videos on LabTube
3,700+ scientific videos
Close
Premium CrownJOIN TECHNOLOGY NETWORKS PREMIUM FREE!