Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Ewing’s sarcoma : Discovery of a "link" in tumor growth

23.09.2004


When cells express the abnormal protein… In these cells, the blue, green and yellow labeling respectively corresponds to the nucleus, the abnormal protein EWS/FLI-1 and the protein IGFBP-3. In the cells where EWS/FLI-1 is present (green labeling), IGFBP-3 is absent (no yellow labeling), confirming that EWS/FLI1 prevents expression of the IGFBP-3 gene. A. Prieur/Institut Curie


To develop new therapeutic approaches to cancer, it is essential to understand the long and extremely complex process that underlies it, in other words the various stages of cancer development from the initial mutation to the tumor. Having already identified the alteration that leads to Ewing’s sarcoma, a bone cancer which afflicts young people, an Inserm team at the Institut Curie has recently used a combination of novel techniques to show that there 86 deregulated genes in these tumors. One of these genes, a new “link” in the development of Ewing’s sarcoma, could be used as a therapeutic target. These discoveries were published in the August 2004 issue of Molecular and Cellular Biology.

Cancer results from the proliferation of abnormal cells in the body. The trigger is an alteration in the genetic material of a single cell, in certain genes that regulate vital processes (division, differentiation, apoptosis, repair). However, a single mutation is not enough to transform a health cell into a cancer cell. Rather it is a succession of genetic accidents that results in uncontrolled cells that accumulate and lead to tumor formation.

Few cancers have a simple molecular signature – a specific mutation that leads to tumor growth. In Ewing’s sarcoma, a malignant tumor of the bone which affects children, teenagers and young adults, this molecular signature has been discovered thanks to a close collaboration between physicians and researchers at the Institut Curie, the internationally renowned reference center for the study and treatment of Ewing’s sarcoma.



Olivier Delattre(1) and his group have identified and characterized this mutation: it arises from an accidental exchange of genetic material between two chromosomes. This leads to the formation of a mutated gene that produces an abnormal protein called EWS/FLI-1 (see box overleaf). To understand the growth of Ewing’s sarcoma, Delattre and colleagues are now studying the effects of EWS/FLI-1 on the cellular machinery. They use an original approach in which the technique of RNA interference(2) is used to “switch off” the mutated gene. The abnormal protein is therefore no longer produced. Using DNA chips, they have studied how other genes are affected by the absence of the abnormal protein.

When a "brake" on proliferation is released…

With this combination of innovative techniques, Delattre and colleagues have identified 86 genes whose expression is altered in the absence of the abnormal protein. They have paid particular attention to one of these genes – the IGFBP-3 gene – whose expression is greatly reduced in tumor cells but which is again expressed normally when the altered protein is absent. The protein produced by the IGFBP-3 gene is known to block one of the most important cellular messengers, insulin-like growth factor 1. IGF-1 controls several fundamental mechanisms such as cellular proliferation and apoptosis (cell death). Overexpression of IGF-1 has, moreover, been implicated in certain cancers.

The Institut Curie researchers have thus shown in Ewing’s sarcoma that the altered protein prevents expression of the IGFBP-3 gene. As a consequence, IGF-1 is no longer "blocked" and so emits a continuous signal ordering the cells to proliferate. IGFBP-3 plays a role upstream in this signaling pathway and could be targeted therapeutically to block IGF-1-induced abnormal cellular proliferation.

Olivier Delattre and his team at the Institut Curie have therefore discovered a new “link” in the growth of Ewing’s sarcoma. Through better comprehension of the cascades of deregulations specific to each tumor, it will be possible to develop new therapeutic strategies that are better targeted and hence more effective.

Catherine Goupillon | alfa
Further information:
http://www.curie.fr
http://mcb.asm.org

More articles from Life Sciences:

nachricht Zebrafish's near 360 degree UV-vision knocks stripes off Google Street View
22.06.2018 | University of Sussex

nachricht New cellular pathway helps explain how inflammation leads to artery disease
22.06.2018 | Cedars-Sinai Medical Center

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Temperature-controlled fiber-optic light source with liquid core

In a recent publication in the renowned journal Optica, scientists of Leibniz-Institute of Photonic Technology (Leibniz IPHT) in Jena showed that they can accurately control the optical properties of liquid-core fiber lasers and therefore their spectral band width by temperature and pressure tuning.

Already last year, the researchers provided experimental proof of a new dynamic of hybrid solitons– temporally and spectrally stationary light waves resulting...

Im Focus: Overdosing on Calcium

Nano crystals impact stem cell fate during bone formation

Scientists from the University of Freiburg and the University of Basel identified a master regulator for bone regeneration. Prasad Shastri, Professor of...

Im Focus: AchemAsia 2019 will take place in Shanghai

Moving into its fourth decade, AchemAsia is setting out for new horizons: The International Expo and Innovation Forum for Sustainable Chemical Production will take place from 21-23 May 2019 in Shanghai, China. With an updated event profile, the eleventh edition focusses on topics that are especially relevant for the Chinese process industry, putting a strong emphasis on sustainability and innovation.

Founded in 1989 as a spin-off of ACHEMA to cater to the needs of China’s then developing industry, AchemAsia has since grown into a platform where the latest...

Im Focus: First real-time test of Li-Fi utilization for the industrial Internet of Things

The BMBF-funded OWICELLS project was successfully completed with a final presentation at the BMW plant in Munich. The presentation demonstrated a Li-Fi communication with a mobile robot, while the robot carried out usual production processes (welding, moving and testing parts) in a 5x5m² production cell. The robust, optical wireless transmission is based on spatial diversity; in other words, data is sent and received simultaneously by several LEDs and several photodiodes. The system can transmit data at more than 100 Mbit/s and five milliseconds latency.

Modern production technologies in the automobile industry must become more flexible in order to fulfil individual customer requirements.

Im Focus: Sharp images with flexible fibers

An international team of scientists has discovered a new way to transfer image information through multimodal fibers with almost no distortion - even if the fiber is bent. The results of the study, to which scientist from the Leibniz-Institute of Photonic Technology Jena (Leibniz IPHT) contributed, were published on 6thJune in the highly-cited journal Physical Review Letters.

Endoscopes allow doctors to see into a patient’s body like through a keyhole. Typically, the images are transmitted via a bundle of several hundreds of optical...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

Munich conference on asteroid detection, tracking and defense

13.06.2018 | Event News

2nd International Baltic Earth Conference in Denmark: “The Baltic Sea region in Transition”

08.06.2018 | Event News

ISEKI_Food 2018: Conference with Holistic View of Food Production

05.06.2018 | Event News

 
Latest News

Graphene assembled film shows higher thermal conductivity than graphite film

22.06.2018 | Materials Sciences

Fast rising bedrock below West Antarctica reveals an extremely fluid Earth mantle

22.06.2018 | Earth Sciences

Zebrafish's near 360 degree UV-vision knocks stripes off Google Street View

22.06.2018 | Life Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>