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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.

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

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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