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INTEGRISTEM TERMINATED

Functions of Integrins in Mammary Stem Cell Activity and Tumorigenesis

Total Cost €

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EC-Contrib. €

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Partnership

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 Outcomes and results

 INTEGRISTEM project word cloud

Explore the words cloud of the INTEGRISTEM project. It provides you a very rough idea of what is the project "INTEGRISTEM" about.

adult    elucidate    receptors    molecular    niche    populations    maintenance    interactions    cells    bipotent    employed    expansion    lobulo    integrin    clonogenic    tumor    gland    whilst    functional    bilayer    expression    progenitors    basement    creloxp    membrane    indicated    alveolar    morphogenesis    myoepithelial    epithelial    capacity    organization    stages    baso    layer    progenitor    mutations    regenerative    tumorigenesis    model    stem    restricted    initiation    abnormal    brca1    regulation    chains    amplification    luminal    depleted    cancer    cytoskeleton    appear    differentiation    layers    ex    understanding    binding    p53    survival    vivo    virgin    producing    cell    mammary    microenvironment    milk    pregnancy    originate    integrins    alpha    developmental    blg    function    epithelium    breast    promoter    organotypic    mouse    analyze    drastic    contain    biologists    polarization    thought    proliferation    hormones    deleted    cultures    lineage    mutant    apical    examined    population    cre    laminin    tumors    glands    mice    activated    normal    notably    basal    tested    puberty   

Project "INTEGRISTEM" data sheet

The following table provides information about the project.

Coordinator		 INSTITUT CURIE 

Organization address
address: rue d'Ulm 26
city: PARIS
postcode: 75231
website: www.curie.fr

contact info
title: n.a.
name: n.a.
surname: n.a.
function: n.a.
email: n.a.
telephone: n.a.
fax: n.a.
 Coordinator Country France [FR]
 Project website https://science.institut-curie.org/research/multiscale-physics-biology-chemistry/umr144-subcellular-structure-and-cellular-dynamics/team-glukhova/
 Total cost 185˙076 €
 EC max contribution 185˙076 € (100%)
 Programme 1. H2020-EU.1.3.2. (Nurturing excellence by means of cross-border and cross-sector mobility)
 Code Call H2020-MSCA-IF-2015
 Funding Scheme MSCA-IF-EF-RI
 Starting year 2016
 Duration (year-month-day) from 2016-05-01   to  2018-04-30

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    INSTITUT CURIE FR (PARIS) coordinator 185˙076.00

Map

 Project objective

Understanding the functional interactions between mammary epithelium and its microenvironment, with a particular focus on the stem cell niche, represents a challenge for developmental and cancer biologists. Mammary epithelium is a bilayer, with a layer of luminal cells, producing milk, and a layer of basal myoepithelial cells. Both layers contain clonogenic stem/progenitor cells, which ensure the drastic epithelial expansion in puberty and pregnancy. Whilst basal stem cells are thought to be bipotent, luminal progenitors appear to be lineage-restricted in normal gland. Recent studies indicated that basal-like breast tumors, notably those with BRCA1 mutations, might originate from luminal progenitors. Our project aims to elucidate the role of integrin receptors for Laminin, major component of the mammary basement membrane, in the regulation of the luminal progenitor function during normal mammary development and tumorigenesis. To this end, α3 and α6 integrin chains were deleted from mammary luminal cells in vivo using CreLoxP system. Cre expression was driven to luminal progenitors by the Blg promoter, activated in this cell population in adult virgin mice and further on, during lobulo-alveolar development in pregnancy. The stem cell activity and the maintenance of the stem cell populations in mutant mammary glands will be analyzed at different developmental stages. Morphogenesis, proliferation, survival, differentiation as well as the regenerative and clonogenic potential of the mutant epithelium will be examined. We will study the cytoskeleton organization and the capacity of mutant cells for baso-apical polarization. To analyze the responses of integrin-depleted cells to hormones and growth factors at the molecular level, organotypic ex vivo cultures will be employed. The impact of Laminin-binding integrins on abnormal luminal progenitor amplification during tumor initiation will be tested in a mouse model of basal-like breast cancer induced by p53 and BRCA1 loss.

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The information about "INTEGRISTEM" are provided by the European Opendata Portal: CORDIS opendata.

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