Corporate Banner
Satellite Banner
Technology
Networks
Scientific Communities
 
Become a Member | Sign in
Home>News>This Article
  News
Return

Tension on Gut Muscles Induces Cell Invasion in Zebrafish Intestine

Published: Wednesday, September 12, 2012
Last Updated: Wednesday, September 12, 2012
Bookmark and Share
Study finds this effect mimics cancer metastasis.

The stiffness of breast tissue is increasingly recognized as an important factor explaining the onset of breast cancer. Stiffening induces molecular changes that promote cancerous behavior in cells. Bioengineering studies have found that breast cancer cells grown on a 3-D gel have enhanced cell replication and decreased organization as rigidity increases. These signals are probably coordinated by surface proteins that communicate with connective tissue, to regulate cell replication, death, and movement. However, very little is known about how stiffness or other physical characteristics of tissues contributes to cancer behavior in living animals.

Towards a better understanding of how tissue stiffness drives cancer, in a new paper published in PLoS Bio this week, Michael Pack, MD, associate professor of Medicine, Perelman School of Medicine, University of Pennsylvania, and colleagues, show that epithelial cells lining the intestine of zebrafish that carry an activating mutation of the smooth muscle myosin gene form protrusions called invadopodia that allow the cells to invade surrounding connective tissue. The epithelial cell protrusions form in response to non-regulated contractions in the surrounding smooth muscle cells. These contractions generate oxidative stress in the epithelial cells, which has been linked to invadopodia formation in human cancer cells. The zebrafish mutant is a novel living model to study how physical characteristics of a tissue can induce cells to invade surrounding tissues, the first step in cancer metastasis.

Epithelial cells of the digestive tract and many other organs are separated from their underlying connective tissue cells by a thin layer of extracellular matrix called the basement membrane. During cell invasion, epithelial cells breach the basement membrane and invade the adjacent connective tissue where the organ's blood vessels and lymphatic channels are located. Invasive cancer cells that are able to enter the blood vessels or lymphatics can migrate to distant tissues thus forming satellite tumors known as metastases.

An important question in cancer research is how invasive cells in living animals correctly localize the enzymes that degrade basement membrane proteins. Investigators have known for some time that many types of cancer cells accomplish this by forming specialized protrusions. It is not known, however, whether these invadopodia are required for cell invasion in living animals or what triggers their formation.

Researchers don't even really know if invadopodia have a normal purpose in healthy tissue. Pack explains that their study was the first to show that invadopodia occur in living animals. This work in live zebrafish is the first direct evidence that invadopodia play a role in tissue cell invasion and identifies the physical signal that drives this process, which in turn, does so by inducing oxidative stress in the invasive cells.

Indeed, eliminating Tks5, a protein required for invadopodia formation in mammalian cells that helps generate reactive oxygen species, blocked formation of the protrusions and rescued mutant zebrafish from cell invasion.

Mouse studies along the same research lines as the zebrafish are planned. The zebrafish and mouse models under development could one day be used to screen potential drugs to stop formation of the errant invadopodia, thus preventing metastases at an early stage of their development. Supporting this idea, mutations in the human smooth muscle myosin genes are present in patients with colorectal cancer and are associated with cancer invasion.

In addition, the team's experiments also point to the possibility that humans who carry a single copy of smooth muscle mutations similar to the zebrafish mutation might inherit a disposition to cancer progression, if they develop a cancer independently of the mutation. The fish with one copy of the mutant gene develop normally but show cell invasion when exposed to drugs that cause oxidative stress, and the risk is greater in fish carrying oncogenes. "This is an interesting finding because oxidative stress is common in cancers and inflammatory conditions that predispose to cancer, such as ulcerative colitis," notes Pack. Co-authors, all from Penn, are Christoph Seiler, Gangarao Davuluri, Joshua Abrams, Fitzroy J. Byfield, and Paul A. Janmey. The research was funded in part by the National Institute of Diabetes and Digestive and Kidney Diseases (Grant DK54942).


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 2,500+ 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

Synthetic DNA Vaccine Against MERS Shows Promise
A novel synthetic DNA vaccine can, for the first time, induce protective immunity against the Middle East Respiratory Syndrome (MERS) coronavirus in animal species.
Friday, August 21, 2015
Cell Aging Slowed by Putting Brakes on Noisy Transcription
Experiments in yeast hint at ways to extend life of some human cells.
Monday, August 03, 2015
Disrupting Cells’ ‘Powerhouses’ Can Lead to Tumor Growth
University of Pennsylvania researchers find that mitochondrial defects have a key role in a cells becoming cancerous.
Monday, July 13, 2015
New Tracking Method Yields Insights into Mitochondrial Dynamics
Scientists from the University of Pennsylvania have devised a powerful new technique that enables the tracking of every mitochondrion as it moves within a cell.
Thursday, July 02, 2015
Classification of Gene Mutations in Neuroblastoma
Penn Medicine and CHOP experts define riskier mutations in neuroblastoma, setting stage for clinical trial.
Tuesday, November 11, 2014
Potential Therapy for Myasthenia Gravis
Penn study demonstrates efficacy of potential therapy for autoimmune disorder of muscle weakness.
Wednesday, October 08, 2014
Center for Advanced Cellular Therapeutics to Rise on Penn Medicine Campus
New facility poised to accelerate the research and development of personalized cellular cancer therapies.
Friday, September 12, 2014
Gum Disease Bacteria Selectively Disarm Immune System, Penn Study Finds
New study shows that bacteria responsible for many cases of periodontitis cause dysbiosis.
Friday, June 13, 2014
Researchers Develop ‘Onion’ Vesicles for Drug Delivery
University of Pennsylvania researchers have shown that dendrimer-based vesicles self-assemble with concentric layers of membranes, much like an onion.
Wednesday, June 11, 2014
Cell Senescence, Aging Related to Epigenetic Changes
One way cells promote tumor suppression is through a process called senescence, an irreversible arrest of proliferation.
Monday, September 02, 2013
Penn Researchers Show Cocaine Addiction Resistance May Be Passed Down from Father to Son
Animal model reveals paternal cocaine use confers protection against rewarding effects of cocaine in male but not female offspring.
Tuesday, December 18, 2012
A Comparative Medicine Study by Penn Vet Identifies a New Approach to Combat Viral Infections
When a virus such as influenza invades our bodies, interferon proteins are among the first immune molecules produced to fight off the attack.
Thursday, November 15, 2012
Pancreatic Cancer Can Run but Not Hide
Immune system tricked into helping cancer cells, but can be blocked, according to Penn study.
Wednesday, June 13, 2012
A Change of Heart: Penn Researchers Reprogram Brain Cells to Become Heart Cells
Researchers at the University of Pennsylvania demonstrate the direct conversion of a non-heart cell type into a heart cell by RNA transfer.
Thursday, July 14, 2011
A New Way to Make Reprogrammed Stem Cells
Penn study eliminates the use of transcription factors and increases efficiency 100-fold.
Wednesday, April 13, 2011
Scientific News
The Changing Tides of the In Vitro Diagnostics Market
With the increasing focus in personalized medicine, diagnostics plays a crucial role in patient monitoring.
LaVision BioTec Reports on the Neuro Research on the Human Brain After Trauma
Company reports on the work of Dr Ali Ertürk from the Institute for Stroke and Dementia Research at LMU Munich.
NIH Study Shows No Benefit of Omega-3 Supplements for Cognitive Decline
Research was published in the Journal of the American Medical Association.
Less May Be More in Slowing Cholera Epidemics
Mathematical model shows more cases may be prevented and more lives saved when using one dose of cholera vaccine instead of recommended two doses.
Investigating the Vape
Expert independent review concludes that e-cigarettes have potential to help smokers quit.
NIH Launches Human RSV Study
Study aims to understand infection in healthy adults to aid development of RSV medicines, vaccines.
Researchers Discover Synthesis of a New Nanomaterial
Interdisciplinary team creates biocomposite for first time using physiological conditions.
Poor Survival Rates in Leukemia Linked to Persistent Genetic Mutations
For patients with an often-deadly form of leukemia, new research suggests that lingering cancer-related mutations – detected after initial treatment with chemotherapy – are associated with an increased risk of relapse and poor survival.
Flu Remedies Help Combat E. coli Bacteria
Physiologists from the University of Zurich have now discovered why the intestinal bacterium Escherichia coli (E. coli) multiplies heavily and has an inflammatory effect.
Marijuana Genome Unraveled
A study by Canadian researchers is providing a clearer picture of the evolutionary history and genetic organization of cannabis, a step that could have agricultural, medical and legal implications for this valuable crop.
Scroll Up
Scroll Down
Skyscraper Banner

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