MICROENVIMET

Understanding and fighting metastasis by modulating the tumour microenvironment through interference with the protease network

 Coordinatore UNIVERSITE DE LIEGE 

 Organization address city: LIEGE
postcode: 4000

contact info
Titolo: Dr.
Nome: Isabelle
Cognome: Halleux
Email: send email
Telefono: +32 4 366 54 28
Fax: +32 4 366 55 58

 Nazionalità Coordinatore Belgium [BE]
 Sito del progetto http://www.microenvimet.eu/
 Totale costo 4˙270˙856 €
 EC contributo 2˙999˙689 €
 Programma FP7-HEALTH
Specific Programme "Cooperation": Health
 Code Call FP7-HEALTH-2007-A
 Funding Scheme CP-FP
 Anno di inizio 2008
 Periodo (anno-mese-giorno) 2008-03-01   -   2012-02-29

 Partecipanti

# participant  country  role  EC contrib. [€] 
1    UNIVERSITE DE LIEGE

 Organization address city: LIEGE
postcode: 4000

contact info
Titolo: Dr.
Nome: Isabelle
Cognome: Halleux
Email: send email
Telefono: +32 4 366 54 28
Fax: +32 4 366 55 58

BE (LIEGE) coordinator 0.00
2    CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE

 Organization address address: Rue Michel -Ange 3
city: PARIS
postcode: 75794

contact info
Titolo: Dr.
Nome: Hélène
Cognome: Faradji
Email: send email
Telefono: +33 493 95 41 90
Fax: +33 4 92 96 03 39

FR (PARIS) participant 0.00
3    HELSINGIN YLIOPISTO

 Organization address address: YLIOPISTONKATU 4
city: HELSINGIN YLIOPISTO
postcode: 14

contact info
Titolo: Ms.
Nome: Katariina
Cognome: Vainio-Mattila
Email: send email
Telefono: +358 9 191 25043
Fax: +358-9-191 25044

FI (HELSINGIN YLIOPISTO) participant 0.00
4    INSTITUT JOZEF STEFAN

 Organization address address: Jamova 39
city: LJUBLJANA
postcode: 1000

contact info
Titolo: Prof.
Nome: Jadran
Cognome: Lenarcic
Email: send email
Telefono: +386 1 477 35 13
Fax: +386 1 477 39 06

SI (LJUBLJANA) participant 0.00
5    KLINIKUM RECHTS DER ISAR DER TECHNISCHEN UNIVERSITAT MUNCHEN

 Organization address address: ISMANINGER STRASSE 22
city: MUENCHEN
postcode: 81675

contact info
Titolo: Prof.
Nome: Achim
Cognome: Krüger
Email: send email
Telefono: +49 89 4140 4463
Fax: +49 89 4140 6182

DE (MUENCHEN) participant 0.00
6    REGION HOVEDSTADEN

 Organization address address: KONGENS VAENGE 2
city: HILLEROD
postcode: 3400

contact info
Titolo: Ms.
Nome: Tove
Cognome: Ostergaard
Email: send email
Telefono: 4535456024
Fax: 4535453797

DK (HILLEROD) participant 0.00
7    UNIVERSIDAD DE OVIEDO

 Organization address address: Calle San Francisco 3
city: OVIEDO
postcode: 33003

contact info
Titolo: Ms.
Nome: Rosa Maria
Cognome: Corujo Quidiello
Email: send email
Telefono: +34 985 104081
Fax: +34 985104040

ES (OVIEDO) participant 0.00
8    UNIVERSITA DEGLI STUDI DI TORINO

 Organization address address: Via Giuseppe Verdi 8
city: TORINO
postcode: 10124

contact info
Titolo: Prof.
Nome: Maria Flavia
Cognome: Di Renzo
Email: send email
Telefono: +39 011 9933343
Fax: +39 011 9933417

IT (TORINO) participant 0.00
9    UNIVERSITAETSKLINIKUM FREIBURG

 Organization address address: HUGSTETTER STRASSE 49
city: FREIBURG
postcode: 79106

contact info
Titolo: Mr.
Nome: Jürgen
Cognome: Dreyer
Email: send email
Telefono: +49 761 2702081
Fax: +49 761 270 1889

DE (FREIBURG) participant 0.00

Mappa


 Word cloud

Esplora la "nuvola delle parole (Word Cloud) per avere un'idea di massima del progetto.

therapeutic    network    manipulation    microenvimet    vitro    cancer    models    pathways    secondary    molecules    breast    efficacy    vivo    metastatic    clinical    stem    proteases    steps    strategies    human    primary    antibodies    model    gene    imaging    cell    tumour    interplay    tumours    modulate    innovative    molecular    metastasis    protease    progression    technologies    regulators    host    identification    inhibitors    microenvironment    cells    cellular   

 Obiettivo del progetto (Objective)

'The MICROENVIMET project proposes innovative approaches for building a comprehensive understanding of the interplay between cancer cells and their microenvironment both at primary and secondary sites. The objectives are to identify molecular pathways involved in the regulation of metastatic dissemination to lung, liver, lymph node and bone. To achieve these objectives, the original experimental approach proposed is to modulate the production/activity of proteases or their inhibitors. Proteases are now recognized as key regulators of a complex network of interacting molecules that modulate the properties of cancer cells and their microenvironment. The project is intended to identify key molecular pathways underlying early steps of metastatic dissemination by interfering with the protease network and studying the impact of such experimentally manipulated microenvironment on metastasis formation. In addition to identifying key regulators of metastasis, we aim at developing blocking antibodies towards these new candidates, with efficacy for therapeutic intervention, by using the most advanced state-of-the-art technologies. The study of cancer stem cells will be integrated into current concepts that consider and attempt to explain the importance of the microenvironment during cancer progression. The 9 academic and 1 SME Participants will combine expertise in genomics, proteomics, bioinformatics, in vivo imaging, transgenic mice, mouse models of metastasis, genetic manipulation of transplantable tumour cells, computerized image analysis, virus-mediated gene transfer, phage display and production of neutralizing antibodies. This consortium will facilitate shared access to a new microRNA platform, innovative technologies, human tumour tissue banks, in vivo and in vitro models mimicking different steps of metastatic dissemination, as well as know how in tumour-host cell interplay, angiogenesis, lymphangiogenesis, cancer stem cell biology and generation of database.'

Introduzione (Teaser)

Failure of diverse clinical approaches to alleviate metastatic spread of neoplastic disease indicates that the process of metastasis is not sufficiently understood. A European study was designed to examine the role of the metastatic niche by investigating the nature and molecular pathways involved.

Descrizione progetto (Article)

The ability of cancer cells to colonise tissues and form new tumours, a process known as metastasis, represents the hallmark of cancer and the major death determinant of cancer patients. Understanding the metastatic dissemination of cancer is vital for designing effective treatment strategies.

By taking into account a variety of cellular and non-cellular factors in the microenvironment within the primary and secondary tumour site, the Microenvimet project was based on the concept that the microenvironment is decisive for tumour progression. In line with this aim, the consortium used innovative approaches to study the interplay between cancer cells and their microenvironment.

In particular, project scientists focused on the network of proteases, enzymes responsible for various cellular functions. They combined the most advanced state-of-the-art technologies for identification of gene signature with in vivo and in vitro gene manipulation, proteomic analysis and in vivo imaging of metastatic cells, with the aim of obtaining a global view of the metastatic process.

The use of a metastatic model of breast cancer led to the identification of small non-coding RNAs which were modulated during cancer progression. Modulation of the tumour microenvironment revealed a protective effect of some protease members (matrix metalloproteinases) produced by host cells and the contribution of cathepsins in the recruitment of host cells in primary tumours, as well as cancer growth and metastasis.

With the aim of developing an anti-metastatic therapy, the consortium characterised neutralising antibodies and developed nanoparticles for the delivery of protease inhibitors. The efficacy of these strategies was demonstrated in vivo in the breast cancer model.

This approach was extended to human monoclonal antibodies against two membrane-bound proteins, one expressed by tumour cells and one produced by stromal cells contributing to the microenvironment. Evaluation of these molecules as therapeutic drugs will reveal the potential of the approach to become translated into clinical practice.

Collectively, the work by the Microenvimet project underlines the complexity of the molecular network involved in the tumour microenvironment. At the same time, it demonstrates the need to gain an in-depth understanding of the metastatic process for efficient cancer eradication.

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