QuiescStemGBM · Studying the role of Quiescent Cancer Stem Cells in GBM development using a novel in vivo cell cycle-based approach
Horizon 2020 — Marie Skłodowska-Curie Actions
- Duration
- 2020-04-01 → 2022-03-31
- EU contribution
- €183,473
- Participants
- 1
- Scheme
- MSCA-IF-EF-ST
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Results in brief
Studying the role of Quiescent Cancer Stem Cells in GBM development using a novel in vivo cell cycle-based approach
The project focused on characterising the cell cycle state (proliferating and quiescent) cancer stem cells (CSCs) are present in glioblastoma multiforme (GBM) and their different contribution to tumor formation, progression, and relapse after therapy. Indeed, the main problem of incurability of GBM is due to the recurrence within 6-9 months after first treatment. Furthermore, the invasive feature makes GBM to be completely removed by surgery. In the past, several studies have attempted to demonstrate what is the role of quiescent cancer cells in the progression and relapse of the disease after therapy but their role in cancer invasion remain unclear. Even if believed such cells are indeed responsible for the incurability of GBM, the clear scientific confirmation needed a new method or tool specifically designed to do so. The project aimed to address such biological questions using an innovative method developed ad hoc for studying CSCs from a cell cycle point-of-view. Indeed, in the previous studies, the lack of proper tools to specifically trace or ablate or in general to focus the investigation on quiescent cells might have contributed to the poor knowledge on their contribution in GBM pathogenesis. The knowledge obtained from this project is important for society because, due to the lack of an efficient therapy, it will be used to identify new therapeutical target to fight aggressive brain cancers. The main results showed the presence of quiescent cells where the cancer cells invade brain, and their functional characterization highlighted their importance for the invasion and spreading of cancer. In addition, we developed a new model of brain cancer using cerebral organoids. This will allow scientific community to use also artificial mini brain cancer to investigate several biological questions reducing the need of animals.
Data: CORDIS, © European Union
Project objective
Glioblastoma (GBM) is the most common and aggressive high-grade primary brain tumour in adults. More than 90% of the patients shows recurrence of the disease with a survival of 2 years despite a multitherapeutic approach consisting of a first surgical resection of the brain lesion followed by radio- and chemo-therapy. GBM patients die because of the cancer relapse that evolve becoming not sensitive to the classical therapies. A sub-population of quiescent/slow cycling cancer stem cells (CSCs) has been proposed to be the origin of the cancer relapse. The features and role of that specific population of CSCs within GBM is still not well characterised. The aim of the proposed project is to first clarify the cell cycle state of CSCs within GBM induced in mouse models in addition to their contribution and role in cancer development. To achieve this goal, I will use a cell cycle-based approach together GBM mouse models to: characterise the cell cycle state of CSCs within tumour (Aim 1); analyse the contribution of quiescent and proliferating CSCs during cancer development and their molecular features using a novel cell cycle-based lineage tracing approach (Aim 2); analyse the effect of selective ablation of each CSCs sub-subpopulation in cancer growth a novel cell cycle-based cellular ablation (Aim 3). Using a cell cycle point of view, the obtained results will be fundamental for the definition and the role of the different CSCs co-existing within glioma. In particular, the findings will open new avenue in the study of the role of quiescent or proliferating cells within GBM and give the possibility to others in the field for testing for example which cells contribute to cancer relapse after the initial tumour treatment (mass debulking and following radio- and chemo-therapy) or even design new drugs targeting specific CSC types.
Original text from CORDIS.
Participants
- UNIVERSITA DEGLI STUDI DI TRENTO · TrentoCoordinatorItaly
Links
- View on CORDIS
- DOI: 10.3030/844677
- https://www.cibio.unitn.it/495/armenise-harvard-laboratory-of-brain-disorders-and-cancer
Data: CORDIS, © European Union