H2020Индивидуална стипендия2017–2019

BRECASTEM · Functional and Molecular Characterisation of Breast Cancer Stem Cells

„Хоризонт 2020“ — Действия „Мария Склодовска-Кюри“

Период: 2017-03-01 → 2019-02-28
Финансиране от ЕС: 183 455 €
Участници: 1
Схема: MSCA-IF-EF-ST

Линиите свързват координатора с партньорите.

Накратко на български

Стемните клетки на рака на гърдата, разпознаваеми по протеина Lgr6, се сравняват с останалите туморни клетки чрез генетично модифицирани мишки. Това помага да се разберат механизмите за устойчивост към химиотерапията и начините за ограничаване на рецидивите.

Този кратък обзор е генериран от изкуствен интелект

Кратко обяснение, генерирано от езиков модел по текста на CORDIS. Оригиналът е по-долу.

Резултати накратко

Functional and Molecular Characterisation of Breast Cancer Stem Cells

Breast cancer is one of the most common cancers worldwide, with over 2 million new cases in 2018. While some breast cancers in the early stages can be cured through surgery and chemotherapy, tumour progression and relapse are more challenging to treat and are responsible for poor prognosis. Therefore, understanding the basic mechanisms driving breast cancer progression and resistance to chemotherapy is imperative for developing new treatment strategies. Previous research has found that some tumour cells are more resistant to chemotherapy than others and some “chemoresistant” cells can regenerate the tumour even if only a few of them remain. These cells are known as cancer stem cells. The host laboratory previously identified a population of cancer stem cells that can initiate luminaltype mammary gland tumours in a mouse model of breast cancer. The cancer stem cells they identified are marked by a protein on their surface called Lgr6, which also exists in humans.The aim of this project was to use genetically engineered mouse models to separate out the tumour cells marked by Lgr6 from the rest of the tumour cells, and determine the molecular differences between the two populations using a technique called RNA sequencing. In conclusion, this project identified genes associated with cancer stem cell behaviour, which in the future might be targeted to inhibit breast cancer relapse.

Текст от CORDIS, на английски · Данни: CORDIS, © Европейски съюз

Цел на проекта

Every organ harbours adult stem cells which have the potential for long-term replication, together with the capacities of self-renewal and multi-lineage differentiation. These stem cells function in tissue homeostasis and contribute to regeneration in response to injury. In addition, many cancers are caused by transforming mutations occurring in tissue-specific progenitor cells. These transformed stem cells harbour long-term proliferative potential and the ability to regenerate tumours consisting of phenotypically heterogeneous cell types. The identities of cancer stem cells (CSCs) that give rise to breast tumours are incompletely understood. The mammary gland is composed of a complex cellular hierarchy, which undergoes most of its development postnatally. To achieve this great plasticity, both stem and progenitor cells play a pivotal role in the extensive tissue remodelling occurring during puberty and pregnancy. Deregulation of stem and progenitor cells is a key event in mammary carcinogenesis. Recently, the host laboratory identified a rare unipotent progenitor cell population in the adult murine mammary gland characterized by the surface protein leucine-rich repeat-containing G-protein coupled receptor 6 (Lgr6). Oncogenic mutations in Lgr6-positive cells led to the formation of luminal mammary gland tumours, and contributed to tumour aggressiveness and maintenance. Conversely, depletion of Lgr6-positive progenitors in mouse luminal breast cancer dramatically impaired tumour growth and morphology. However, the underlying molecular mechanisms driving these observations are unknown. The aim of this project is the characterisation of Lgr6-positive breast cancer stem cells, using functional and molecular approaches. We will characterise the molecular differences between cancer stem cells and non-stem cells, with the ultimate goal of identifying novel therapeutic strategies to eliminate breast cancer stem cells.

Оригинален текст от CORDIS (на английски).

Участници

THE FRANCIS CRICK INSTITUTE LIMITED · LondonКоординаторОбединеното кралство