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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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 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.

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

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

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 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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