(Press-News.org) The imaging of tumour growth in zebrafish has revealed for the first time how newly formed cancer cells have the capacity to co-opt the immune system into spreading the disease, leading the way for investigations into potential therapies for eliminating early-stage cancer in humans. Using different coloured fluorescent tags, scientists at the University of Bristol labelled immune cells and tumour-forming cells in the translucent zebrafish in order to track their behaviour and interactions by live cell imaging. These dramatic findings, which are the result of a collaboration between academic colleagues in the UK (University of Bristol and University of Manchester) and Italy (Institute of Molecular Oncology, Milan) will publish next week in the online, open access journal PLoS Biology.
Tests showed that cancer cells are less likely to proliferate if white blood cells can be prevented from contacting the precursor cancer cells, suggesting that white blood cells – the immune cells – have the ability to promote disease by providing some kind of growth signal. Interestingly, the chemical compound that acts as a draw between the two sets of cells was shown here to be hydrogen peroxide – commonly used as a disinfectant or antiseptic, but also a natural by-product produced by the body's metabolic process.
Describing the work, Paul Martin, Professor of Cell Biology at the University of Bristol's Schools of Biochemistry and Physiology & Pharmacology, who supervised post-doctoral fellow Yi Feng in the research project, said: "By visualizing the earliest interactions between cancer cells and their host environment, we have shown that even from their earliest stages tumours don't just avoid being destroyed by the immune system. Rather, they appear to court an immune response, co-opting the body's innate immune system to aid and abet their growth."
The team used a method to switch on the human oncogene, HRAS, in specific pigment cells (melanocytes) in the skin of early stage zebrafish embryos. Studies were carried out using zebrafish because they conserve many of the molecular and cellular components of tumour formation seen in mammals and are almost translucent, making it easy to see the cells as they move around and grow. Researchers monitored the first hours and days of development and as the embryo grew, some of the cells were transformed, ie, made cancerous by HRAS. Those transformed cells were found to actively attract the innate immune cells. The researchers got the same results, after inserting HRAS into different, mucous-secreting cells, and again when experimenting with a different oncogene, SRC. They discovered that the tumour cells produced hydrogen peroxide and that immune cells were drawn up the hydrogen peroxide gradient towards the cancer.
The researchers' movies show that the immune cells appear to engulf cancerous cells in a bid to destroy them. However, other cells formed cytoplasmic tethers linking them to cancerous cells and in some cases the cancerous cells appeared to drag the immune cells back when they started to leave the region. In order to see whether the tumour was avoiding destruction or actually co-opting the immune cells, the researchers blocked the immune response in three different ways: they prevented the development of immune cells for the first three days of the zebrafish embryos' life, and separately, they used two different strategies to limit hydrogen peroxide production. In each case, immune cells failed to migrate to the cancer site. And each time, when the immune response was blocked, fewer cancer cells formed.
Professor Martin added: "Yi's movies in Zebrafish larvae give us the first insight into how immune cells sense and then attempt to deal with the earliest stages of cancer. Now we can look closer to discover why it is that immune cells seem to aid growth of these young cancer cells and figure out ways for guiding immune cells how better to search and destroy."
INFORMATION:
Funding: The Martin lab is funded by the Wellcome Trust (Ref 077988/Z/05/Z). AH is funded by a Cancer Research UK Career Development Fellowship (C11876/A4495). MM is supported by The Cariplo Foundation (grant No 2007-5500), and CS is funded by an AICR fellowship. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Competing interests statement: The authors declare that no competing interests exist.
Citation: Feng Y, Santoriello C, Mione M, Hurlstone A, Martin P (2010) Live Imaging of Innate Immune Cell Sensing of Transformed Cells in Zebrafish Larvae: Parallels between Tumor Initiation and Wound Inflammation. PLoS Biol 8(12): e1000562. doi:10.1371/journal.pbio.1000562
PLEASE ADD THE LINK TO THE PUBLISHED ARTICLE IN ONLINE VERSIONS OF YOUR REPORT: http://biology.plosjournals.org/perlserv/?request=get-document&doi=10.1371/journal.pbio.1000562
PRESS ONLY PREVIEW OF THE ARTICLE: http://www.plos.org/press/plbi-08-12-Martin.pdf
RELATED SYNOPSIS: http://www.plos.org/press/plbi-08-12-MartinSynopsis.pdf
CONTACT:
Aliya Mughal
University of Bristol, Public Relations Office
Aliya.Mughal@bristol.ac.uk
END
Using automated screening techniques developed by pharmaceutical companies to find new drugs, researchers from UC San Diego and three other research institutions have discovered a molecule with the most potent effects ever seen on the biological clock. Dubbed "longdaysin," for its ability to dramatically slow down the biological clock, the new compound could pave the way for a host of new drugs to treat severe sleep disorders or quickly reset the biological clocks of jet-lagged travelers who regularly travel across multiple time zones. The researchers demonstrated the dramatic ...
Neonatal intensive care provides substantial population health benefits in Mexico relative to its costs, even for very premature babies, and as such offers exceptional value for money within the country's Popular Health Insurance (Seguro Popular) program, which offers free access to a specific set of health care interventions. Furthermore, neonatal intensive care could also be cost effective in other middle-income countries. These are the findings of a study by Jochen Profit from Baylor College of Medicine, Houston, USA, Joshua Salomon from the Harvard School of Public ...
Jeremy Keenan and colleagues report that during a cluster-randomized clinical trial in Ethiopia, nasopharyngeal pneumococcal resistance to macrolides was significantly higher in communities randomized to receive azithromycin compared with untreated control communities.
Funding: The National Institutes of Health (NEI U10 EY016214) was the main supporter of this trial. This project was also supported by the Bernard Osher Foundation, That Man May See, the Harper Inglis Trust, the Bodri Foundation, the South Asia Research Fund, Research to Prevent Blindness, NIH/NCRR/OD UCSF-CTSI ...
Washington, DC — Monkeys moved thought-controlled computer cursors more quickly and accurately when provided with additional sensory feedback, according to a new study in the Dec. 15 issue of The Journal of Neuroscience. While most brain-machine technologies rely only on visual feedback, this study demonstrated that these systems can be improved when users have additional input, such as a sense of the arm's position and motion, a sensation known as proprioception.
With the aid of brain-controlled devices, paralyzed people have been able to send e-mail, ...
Inside a small cabinet the size of a dorm refrigerator in one of Himadri B. Pakrasi's labs, a blue-green soup percolates in thick glass bottles under the cool light of red, blue and green LEDS.
This isn't just any soup, however. It is a soup of champions.
The soup is colored by a strain of blue-green bacteria that bubble off roughly 10 times the hydrogen gas produced by their nearest competitors—in part because of their unique genetic endowment but also in part because of tricks the scientists have played on their metabolism.
Hydrogen gas can be produced by microbes ...
DALLAS – Dec. 14, 2010 – Researchers at UT Southwestern Medical Center have discovered sets of genes active in cancer cells and normal tissue that predict survival time and potential new treatments for patients with non-small cell lung cancer.
"Patient responses to cancer treatment vary widely and often depend on subtle biological differences among tumors," said Dr. David Mangelsdorf, chairman of pharmacology at UT Southwestern and co-lead author of the study, published Dec. 14 by PLoS Medicine.
"These findings are important because the ability to determine which genes ...
If you want to look attractive and healthy, the best thing you can do is get a good night's sleep, finds research in the Christmas issue published on bmj.com today.
For the first time, say the authors, there is scientific backing for the concept of beauty sleep.
The study, led by John Axelsson from the Karolinska Institutet in Sweden, investigated the relationship between sleep and perceptions of attractiveness and health. The authors believe this research is important in today's 24 hour society with the number of people suffering from sleep disorders and disturbed ...
People can be reassured that while alcohol may slow down digestion after a rich calorific meal, enjoyed by many during the Christmas season, it will not cause indigestion symptoms such as heartburn, belching and bloating, finds research in the Christmas issue published on bmj.com today.
In order to determine the effects of alcohol on the digestive system when rich meals are consumed, investigators at the University Hospital of Zurich, led by Dr Mark Fox now at the Queens Medical Centre in Nottingham, studied 20 individuals who either drank wine or black tea with cheese ...
Research in the Christmas issue published on bmj.com today explodes the Danish myth that it is possible to get drunk by submerging your feet in alcohol.
The authors, led by Dr Peter Lommer Kristensen from the Hillerød Hospital in Denmark, say it was important that the myth underwent scientific scrutiny to prevent students wasting their time experimenting with this activity.
Three adult volunteers took part in the study. None of them suffered from any chronic skin or liver disease and they were not addicted to alcohol or psychoactive drugs. The participants were not ...
The skeletons of kings and queens lying in mass graves in the Royal Basilica of Saint-Denis in Paris could finally have the solemn funeral ceremonies they deserve, say experts in the Christmas issue published on bmj.com today.
Many of the graves in the Royal Basilica were destroyed by revolutionaries in 1793 and very few remains of the mummified bodies have been preserved and identified.
Dr Philippe Charlier led the scientific breakthrough that has identified the head of the French King, Henri IV.
A team of scientists from different fields of expertise including ...
