Project

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Cancer Stem Cells and metastasis: control of cell fate decisions through crosstalk with their lineage and the microenvironment.

Applicant Santamaria-Martínez Albert
Number 154751
Funding scheme Ambizione
Research institution Unité de Pathologie Faculté de Science et Médecine Université de Fribourg
Institution of higher education University of Fribourg - FR
Main discipline Experimental Cancer Research
Start/End 01.06.2015 - 31.12.2018
Approved amount 595'919.00
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All Disciplines (3)

Discipline
Experimental Cancer Research
Cellular Biology, Cytology
Molecular Biology

Keywords (3)

metastasis; niche; cancer stem cells

Lay Summary (French)

Lead
Les cellules souches cancéreuses (CSCs) sont au sommet de la hiérarchie tumorale. Elles sont à l'origine des tumeurs primaires et de leurs métastases, qui causent 90% des décès dûs au cancer, et sont aussi responsables des récidives. À ce jour, aucune étude n'a réussi à démontrer si l'élimination des CSCs est suffisante pour éradiquer la tumeur en entier. Ce projet apporte une contribution à ce domaine de recherche.
Lay summary

Titre du projet

Cellules souches cancéreuses et métastases.

Introduction

Au cours des dernières années, les biologistes du cancer ont proposé une nouvelle explication au sujet de l'origine des tumeurs, selon laquelle certains cancers sont le résultat de la transformation de cellules souches normales spécifiques d'un tissu en cellules cancéreuses. Les principales caractéristiques d'une cellule souche sont la génération d’une copie exacte d'elle-même ainsi que de la génération d'autres types de cellules filles par différentiation. Plusieurs études ont constaté que dans certaines tumeurs, les cellules qui présentent les caractéristiques mentionnées ci-dessus sont présentes, d'où leur appellation de cellules souches cancéreuses (CSCs).

Contenu et objectifs du travail de recherche

Ces CSCs sont au sommet de la hiérarchie tumorale et par conséquent sont responsables de produire (et reproduire) la tumeur, comprenant différents types de cellules. Le but de ce projet est de démontrer expérimentalement si l'éradication des CSCs est suffisante pour éliminer les tumeurs du cancer du sein (tumeurs primaires et métastases). Pour atteindre cet objective, des modèles expérimentaux et des techniques de génie génétique, conçus à cet effet, vont être employés. De plus, l'étude portera aussi sur les interactions entre les CSCs et d'autres populations de cellules, principalement les cellules filles, ainsi que sur l'environnement dans lequel ces cellules vivent et sur la façon dont ces facteurs affectent la progression tumorale.

Contexte scientifique et social du projet de recherche

Le projet relève de la recherche translationnelle. Les résultats de ce projet aideront à comprendre l'organisation et le fonctionnement des tumeurs, ce qui est nécessaire pour proposer des stratégies thérapeutiques plus efficaces.

 

Mots-clés

Cancer, métastase, cellule souche, cellules souches cancéreuses.

 

 

 

Direct link to Lay Summary Last update: 03.03.2015

Responsible applicant and co-applicants

Employees

Publications

Publication
The Tumor Microenvironment as a Driving Force of Breast Cancer Stem Cell Plasticity
Fico Flavia, Santamaria-Martínez Albert (2020), The Tumor Microenvironment as a Driving Force of Breast Cancer Stem Cell Plasticity, in Cancers, 12(12), 3863-3863.
TGFBI modulates tumour hypoxia and promotes breast cancer metastasis
Fico Flavia, Santamaria‐Martínez Albert (2020), TGFBI modulates tumour hypoxia and promotes breast cancer metastasis, in Molecular Oncology, 1878-0261.-1878-0261..
Intestinal Stem CellsMethods and Protocols
Dafflon Caroline, Santamaria-Martínez Albert, Ordóñez-Morán Paloma (2020), Intestinal Stem CellsMethods and Protocols, Springer US, New York, NY.
MAGI1, a New Potential Tumor Suppressor Gene in Estrogen Receptor Positive Breast Cancer
Alday-Parejo Begoña, Richard François, Wörthmüller Janine, Rau Tilman, Galván José A., Desmedt Christine, Santamaria-Martinez Albert, Rüegg Curzio (2020), MAGI1, a New Potential Tumor Suppressor Gene in Estrogen Receptor Positive Breast Cancer, in Cancers, 12(1), 223-223.
Breast Cancer Stem Cells with Tumor- versus Metastasis-Initiating Capacities Are Modulated by TGFBR1 Inhibition
Fico Flavia, Bousquenaud Mélanie, Rüegg Curzio, Santamaria-Martínez Albert (2019), Breast Cancer Stem Cells with Tumor- versus Metastasis-Initiating Capacities Are Modulated by TGFBR1 Inhibition, in Stem Cell Reports, 1-9.
Obesity promotes the expansion of metastasis-initiating cells in breast cancer
Bousquenaud Mélanie, Fico Flavia, Solinas Giovanni, Rüegg Curzio, Santamaria-Martínez Albert (2018), Obesity promotes the expansion of metastasis-initiating cells in breast cancer, in Breast Cancer Research, 20(1), 104-104.

Collaboration

Group / person Country
Types of collaboration
Cancer Stem Cell Lab/ISREC-EPFL Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
- Research Infrastructure
Experimental and Translational Oncology Lab/ University of Fribourg Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
- Research Infrastructure
- Exchange of personnel

Scientific events

Active participation

Title Type of contribution Title of article or contribution Date Place Persons involved
Breakthroughs in cancer research and therapy 2019 Poster Modulation of breast CSC with tumor vs metastasis initiating capacities. 30.01.2019 Zürich, Switzerland Santamaria-Martínez Albert;
Breakthroughs in cancer research and therapy 2019 Poster Modulatory activities of the extracellular matrix on breast cancer stem cells. 30.01.2019 Zürich, Switzerland Santamaria-Martínez Albert;
ISREC-SCCL Symposium 2018: Horizons of Cancer Biology & Therapy Poster Modulatory activities of the extracellular matrix on cancer stem cells in breast cancer 08.09.2018 SwissTech Convention Center, Lausanne, Switzerland Santamaria-Martínez Albert;
The Stem Cell Niche Poster A novel mechanism controlling cancer stem cells in breast cancer 27.05.2018 Favrholm Campus, Roskildevej 58, DK-3400 Hillerød, Denmark Santamaria-Martínez Albert;
ENBDC workshop Methods in mammary gland biology and breast cancer Talk given at a conference Cancer stem cells immunomodulatory activities shape the fate of breast tumors 15.03.2018 Weggis, Switzerland Santamaria-Martínez Albert;
7th International Conference on Tumor-Host Interaction and Angiogenesis Talk given at a conference A new mechanism controlling cancer stem cells in breast cancer 25.06.2017 Ascona, Switzerland Santamaria-Martínez Albert;
The Master in Experimental Biomedical Research (EBR) Individual talk Cancer Stem Cells 16.03.2017 Fribourg, Switzerland Santamaria-Martínez Albert;
Breakthroughs in cancer research and therapy 2017 Poster TGFBI controls cancer stem cell fate in breast cancer 01.02.2017 Zurich, Switzerland Santamaria-Martínez Albert;
ISREC-SCCL Symposium 2016: Horizons of Cancer Biology & Therapy Poster Therapeutic overactivation of the oxidative pentose phosphate pathway depletes breast cancer stem cells. 07.09.2016 Lausanne, Switzerland Santamaria-Martínez Albert;
The Master in Experimental Biomedical Research (EBR) Individual talk Cancer Stem Cells 08.03.2016 Fribourg, Switzerland Santamaria-Martínez Albert;


Self-organised

Title Date Place
The Master in Experimental Biomedical Research (EBR) 01.03.2018 Fribourg, Switzerland

Communication with the public

Communication Title Media Place Year
Talks/events/exhibitions 7th Research day in medicine German-speaking Switzerland Western Switzerland 2018
Talks/events/exhibitions University of Fribourg Research Day Western Switzerland German-speaking Switzerland 2017

Abstract

Over 90% of cancer-related deaths are due to metastatic disease. Metastasis is a very ineffective process that consists of a series of rate-limiting sequential events that culminate with the colonization and destruction by tumor cells of a different environment. It is now accepted that tumors, as other healthy tissues, are organized as a hierarchy in which cancer stem cells (CSC) are at the apex. It has been recently shown that CSCs are not only responsible for tumor development and resistance to therapy, but are also the cell-of-origin of metastasis. Therefore, understanding the mechanisms that CSCs use in order to colonize secondary organs is of paramount importance to the field of cancer biology. The goals of this project are to understand 1) the reasons why it is necessary and sufficient to kill only CSCs to eradicate a tumor, i.e. to study the dependence of tumor organization on CSCs; 2) the interactions CSCs establish with other populations of cells in order to colonize secondary organs and maintain the organization of a tumor; and 3) how the balance between pro-tumorigenic and anti-tumorigenic factors in the extracellular matrix can affect colonization by influencing CSCs. To carry out these investigations, both in vitro and in vivo models (mouse models) will be used, with a main focus on metastasis in breast cancer. Overall, these studies will help to shed some light on our comprehension of the metastatic process and will also hopefully help to improve current therapies.
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