Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

2D images as the new tool for cancer prevention

01.12.2014

Portuguese researchers have developed a new method, which from images of a protein in a population of cells quantifies its distribution (how much there is, and where in the cell) for that population. The discovery by researchers João Sanches, Raquel Seruca and colleagues has important medical implications since the cellular location of a protein is directly linked to its function.

This was clear when the new algorithm was tested on cells with mutated e-cadherin (a tumour suppressor protein) where it identified the mutations that produced malfunctioning e-cadherin that causes human diffuse gastric cancer (HDGC), effectively pinpointing the patients at risk of the disease.


2D images identify gastric cancer-prone mutations

The result is particularly important because HDGC is asymptomatic and, at the moment, its early detection is not reliable what means that the disease still has extremely high mortality. The new algorithm with its ability to identify patients at high risk, hopefully, will change that.

The study, out in the European Journal of Human Genetics, is a collaboration between João Sanches from the Institute for Systems and Robotics and Department of Bioengineering from the Instituto Superior Técnico at the Technical University of Lisbon that developed the algorithm, and the group of Raquel Seruca from the Department of Cancer Genetics of IPATIMUP - Institute of Molecular Pathology and Immunology at the University of Porto that works in cancer.

Gastric cancer is the 4th most common cause of cancer in the world, and hereditary diffuse gastric cancer (HDGC) makes up to 3% of all cases. Although not very frequent, the disease is hugely problematic for clinicians because of its high mortality, which is the result of several issues.

First, the fact that HDGC is caused by functional abnormalities/mutations in e-cadherin, an adhesion protein of epithelial cells (those covering the surfaces and inside of the body). E-cadherin holds epithelial cells together by lying across the cell membrane, one end attached to e-cadherins from neighbouring cells and the other to the skeleton of the epithelial cell.

When e-cadherin stops working, the cells become loose. In the case of HDGC, this means that there is no solid tumour, but, instead, a loose layer of cancerous cells, which easily move spreading the disease and making its control impossible unless detection occurs early. This is also why e-cadherin is known as an important tumour suppressor molecule.

The second problem when trying to control the disease is the difficulty of spotting HDGC early. In fact its initial symptoms are very non-specific (stomach acidity and burping for example), so easy to miss. And without clear symptomology, early detection relies on searching gastric cells for lack of e-cadherin on the membrane (a malfunctioning e-cadherin also leaves the membrane to go inside the cell to be destroyed) with results that are not always reliable.

As consequence there has been a major effort to improve HDGC detection, and it is here that Sanches’ algorithm steps in. This new method has many advantages - it is semi-automated what allows, on one hand, the human operators to resort to their experience to choose the more representative cells, and on the other to rely on the computer to normalise results from cells with very different sizes and shapes, and work even with very heterogeneous cell populations. Resorting to images assured that the cells were hardly altered. All of these secured that the results were accurate and representative.

But how did it actually work? The software was designed to compute data from fluorescence images of the protein in a cell population, to generate “maps” of the protein distribution in that population. From these, it constructed 2D virtual images of a “typical cell” in that population, and it also calculated a new parameter called maximum mean ratio (MMR), which quantifies the sharpness of the protein fluorescence peak (so effectively measures the protein quantity). In HDGC experiments, a high MMR meant that e-cadherin has high expression by the membrane (as it should), and low levels inside of the cell

To see if this data could be used to improve the clinical management of HDGC, next, the researchers used the algorithm to compare cells with working e-cadherins, with those carrying mutations that made the protein non-functional/useless (so cancer prone). The idea was, that since normal e-cadherin is on the membrane and its malfunctioning form moves inside the cell to be destroyed, the new algorithm, by giving e-cadherin location, should be able to identify the individuals at risk of HDGC.

And in fact, after constructing 2D images of the two types of cells, the distinction was clear. While normal cells (or those with neutral/innocuous mutations) produced an image of a fluorescence circle with a clear centre (which represented the absence of protein inside the cell), those with malfunctioning e-cadherin (that can lead to HDGC) showed a full fluorescence circle (the fluorescence in the centre represented e-cadherin inside cell).

Additionally, these last cells had much lower MMR than normal, meaning less e-cadherin by the membrane and, in consequence, a weaker cell-to-cell adhesion what agreed with their propensity to cancer. “Our algorithm was not only able to pinpoint the protein location, but also to quantify it in each cellular compartment. While the MMR value gave us the protein dispersion.” - says Seruca

In conclusion, with a combination of 2D images and quantitative “maps” should now be much easier for researchers (and in the future clinicians) to quickly and reliably identify those individuals with mutations that lead e-cadherin to lose its function, and who, as result, are prone to develop HDGC, and who should be put under close monitoring for early signs of disease.

“Our algorithm can now be used as a complementary approach to evaluate the pathogenicity of E-cadherin.”- says Seruca - “Moreover, it can be applied to a wide range of proteins and, more importantly, to diseases characterized by aberrant protein expression or trafficking deregulation. “

And although the study has focused on HDGC, e-cadherin mutations are known to be involved in a variety of other cancers including breast, colorectal, thyroid and ovarian so these new results could also be applied to them.


http://www.nature.com/ejhg/journal/vaop/ncurrent/full/ejhg2014240a.html

Full bibliographic information

European Journal of Human Genetics (2014), 1–8
Quantification of mutant E-cadherin using bioimaging analysis of in situ fluorescence microscopy. A new approach to CDH1 missense variants
João Miguel Sanches, Joana Figueiredo, Martina Fonseca1, Cecília Durães, Soraia Melo, Sofia Esménio and Raquel Seruca*

Catarina Amorim | AlphaGalileo

More articles from Medical Engineering:

nachricht Visualizing gene expression with MRI
23.12.2016 | California Institute of Technology

nachricht Illuminating cancer: Researchers invent a pH threshold sensor to improve cancer surgery
21.12.2016 | UT Southwestern Medical Center

All articles from Medical Engineering >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Quantum optical sensor for the first time tested in space – with a laser system from Berlin

For the first time ever, a cloud of ultra-cold atoms has been successfully created in space on board of a sounding rocket. The MAIUS mission demonstrates that quantum optical sensors can be operated even in harsh environments like space – a prerequi-site for finding answers to the most challenging questions of fundamental physics and an important innovation driver for everyday applications.

According to Albert Einstein's Equivalence Principle, all bodies are accelerated at the same rate by the Earth's gravity, regardless of their properties. This...

Im Focus: Traffic jam in empty space

New success for Konstanz physicists in studying the quantum vacuum

An important step towards a completely new experimental access to quantum physics has been made at University of Konstanz. The team of scientists headed by...

Im Focus: How gut bacteria can make us ill

HZI researchers decipher infection mechanisms of Yersinia and immune responses of the host

Yersiniae cause severe intestinal infections. Studies using Yersinia pseudotuberculosis as a model organism aim to elucidate the infection mechanisms of these...

Im Focus: Interfacial Superconductivity: Magnetic and superconducting order revealed simultaneously

Researchers from the University of Hamburg in Germany, in collaboration with colleagues from the University of Aarhus in Denmark, have synthesized a new superconducting material by growing a few layers of an antiferromagnetic transition-metal chalcogenide on a bismuth-based topological insulator, both being non-superconducting materials.

While superconductivity and magnetism are generally believed to be mutually exclusive, surprisingly, in this new material, superconducting correlations...

Im Focus: Studying fundamental particles in materials

Laser-driving of semimetals allows creating novel quasiparticle states within condensed matter systems and switching between different states on ultrafast time scales

Studying properties of fundamental particles in condensed matter systems is a promising approach to quantum field theory. Quasiparticles offer the opportunity...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Sustainable Water use in Agriculture in Eastern Europe and Central Asia

19.01.2017 | Event News

12V, 48V, high-voltage – trends in E/E automotive architecture

10.01.2017 | Event News

2nd Conference on Non-Textual Information on 10 and 11 May 2017 in Hannover

09.01.2017 | Event News

 
Latest News

Tracking movement of immune cells identifies key first steps in inflammatory arthritis

23.01.2017 | Health and Medicine

Electrocatalysis can advance green transition

23.01.2017 | Physics and Astronomy

New technology for mass-production of complex molded composite components

23.01.2017 | Process Engineering

VideoLinks
B2B-VideoLinks
More VideoLinks >>>