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

A Microchip for Metastasis

Published: Thursday, February 06, 2014
Last Updated: Thursday, February 06, 2014
Bookmark and Share
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. 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 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.


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 3,000+ scientific posters on ePosters
  • More than 4,500+ 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

Long-Term Drug Release
New tablet attaches to the lining of the GI tract, resists being pulled away.
Thursday, April 07, 2016
Cancer Cells Remodel Environments Before Spreading
Researchers at MIT have found that the cancer cells remodel their environment to make it easier to reach nearby blood vessels.
Wednesday, March 16, 2016
Paving the Way for Metastasis
Cancer cells remodel their environment to make it easier to reach nearby blood vessels.
Tuesday, March 15, 2016
Curing Disease by Repairing Faulty Genes
New delivery method boosts efficiency of CRISPR genome-editing system.
Wednesday, February 03, 2016
No More Insulin Injections?
Encapsulated pancreatic cells offer possible new diabetes treatment.
Tuesday, January 26, 2016
Engineering Foe into Friend
Bose Grant awardee Jacquin Niles aims to repurpose the malaria parasite for drug delivery.
Monday, January 25, 2016
Supply Chain
Chemists discover how a single enzyme maintains a cell’s pool of DNA building blocks.
Wednesday, January 13, 2016
How Cancer Cells Spread
Study offers new targets for drugs that may prevent cancer from spreading.
Thursday, December 17, 2015
Delivering microRNAs for Cancer Treatment
Scientists exploit gene therapy to shrink tumors in mice with an aggressive form of breast cancer.
Wednesday, December 09, 2015
Using Ultrasound to Improve Drug Delivery
New approach could aid in treatment of inflammatory bowel disease.
Friday, October 23, 2015
Drug-Resistance Mechanism in Tumor Cells Unravelled
Targeting the RNA-binding protein that promotes resistance could lead to better cancer therapies.
Friday, October 23, 2015
Biologists Find Unexpected Role for Amyloid-Forming Protein
Yeast protein could offer clues to how Alzheimer’s plaques form in the brain.
Monday, September 28, 2015
Viruses Join Fight Against Harmful Bacteria
Engineered viruses could combat human disease and improve food safety.
Friday, September 25, 2015
Targeting DNA
Protein-based sensor could detect viral infection or kill cancer cells.
Tuesday, September 22, 2015
A Metabolic Master Switch Underlying Human Obesity
Researchers find pathway that controls metabolism by prompting fat cells to store or burn fat.
Friday, August 21, 2015
Scientific News
Turning Skin Cells into Heart, Brain Cells
In a major breakthrough, scientists at the Gladstone Institutes transformed skin cells into heart cells and brain cells using a combination of chemicals.
Detection of HPV in First-Void Urine
Similar sensitivity of HPV test on first void urine sample compared to cervical smear.
Potential “Good Fat” Biomarker
New method to measure the activity of energy consuming brown fat cells could ease the testing weight loss drugs.
Shape Of Tumor May Affect Whether Cells Can Metastasize
Illinois researchers found that the shape of a tumor may play a role in how cancer cells become primed to spread.
MicroRNA Pathway Could Lead to New Avenues for Leukemia Treatment
Cancer researchers at the University of Cincinnati have found a particular signaling route in microRNA (miR-22) that could lead to targets for acute myeloid leukemia, the most common type of fast-growing cancer of the blood and bone marrow.
Analysis of Dog Genome will Provide Insight into Human Disease
An important model in studying human disease, the non-coding RNA of the canine genome is an essential starting point for evolutionary and biomedical studies – according to a new study led by The Genome Analysis Centre (TGAC).
New Blood Test for The Earlier Diagnosis of Breast Cancer Spread
Researchers at University of Westminster have confirmed that a new blood test can detect if breast cancer has spread to other parts of the body.
First Gene Therapy Successful Against Human Aging
American woman gets biologically younger after gene therapies.
Targeting an ‘Undruggable’ Cancer Gene
RAS genes are mutated in more than 30 percent of human cancers and represent one of the most sought-after cancer targets for drug developers.
Altered Metabolism of Four Compounds Drives Glioblastoma Growth
Findings suggest new ways to treat the malignancy, slow its progression and reveal its extent more precisely.
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
3,000+ scientific and medical posters
A library of 2,500+ scientific videos on LabTube
4,500+ scientific videos
Close
Premium CrownJOIN TECHNOLOGY NETWORKS PREMIUM FOR FREE!