META2 · METAbolism of bone METAstasis (META2): Metabolic interactions between disseminated breast cancer cells and osteoblast lineage cells drive bone metastases formation
Horizon 2020 — Marie Skłodowska-Curie Actions
- Duration
- 2019-06-01 → 2021-05-31
- EU contribution
- €178,320
- Participants
- 1
- Scheme
- MSCA-IF-EF-ST
Lines connect the coordinator with its partners.
Results in brief
METAbolism of bone METAstasis (META2): Metabolic interactions between disseminated breast cancer cells and osteoblast lineage cells drive bone metastases formation
Breast cancer often metastasize to the bone, resulting in progressive bone destruction and severe complications for the patient. Cancer cells colonize the bone already much earlier, but they often stay dormant for several years and remain undetectable. Recent studies showed that at this early stage, cancer cells are in close proximity to bone-forming cells (osteoblasts), and this interaction promotes their survival and proliferation. Interestingly, recent findings also indicate that the way tumor cells use nutrient – cell metabolism - not only drives primary tumor growth, but also determines which cells will metastasize to lung or liver, indicating metabolic interactions of cells with their microenvironment. This concept may also apply to breast cancer in bone, but insight in the metabolism of cells colonizing the bone is lacking. I hypothesize that to survive and thrive in the bone cells rely on a specific profile that is complementary in nutrient needs to osteoblasts. Thus, my objective is to characterize the metabolism of breast cancer cells in bone at early time points and to validate that targeting this metabolism will limit or prevent bone metastasis. To this end, I will combine metabolomics and transcriptomics on in vivo and in vitro models to identify important metabolic enzymes that will then be validated in in vivo models and human samples. This better understanding of the metabolism of cancer cells in the bone is essential for the development of new diagnostic tools and therapeutic targets.
Data: CORDIS, © European Union
Project objective
Triple negative breast cancer cells (TNBC) metastasize to the bone, resulting in progressive bone destruction and severe complications for the patient. TNBC colonize the bone already much earlier, but they often stay dormant for several years and remain undetectable. Recent studies showed that at this early stage, TNBC cells are in close proximity to bone-forming cells (osteoblasts), and this interaction promotes TNBC survival and proliferation. Interestingly, recent findings also indicate that the metabolism of tumor cells not only drives primary tumor growth, but also determines which cells will metastasize to lung or liver, indicating metabolic interactions of TNBC with their microenvironment. This concept may also apply to TNBC in bone, but insight in the metabolism of TNBC colonizing the bone is lacking. I hypothesize that to survive and thrive in the bone TNBC cells rely on a specific profile that is complementary in nutrient needs to osteoblasts. Accordingly, preliminary results of the lab showed that targeting glutamine pathway impaired bone metastasis formation. Thus, my objective is to characterize the metabolism of TNBC in bone at early time points and to validate that targeting this metabolism will limit or prevent bone metastasis. I will first perform metabolite dosage and transcriptomics on TNBC recovered at early stages of preclinical (mouse) models of bone metastasis. In parallel, I will decipher metabolic interactions in vitro between osteoblasts and TNBC using metabolomics. These two complimentary approaches will deliver fundamental insights into metabolic adaptations of TNBC during bone metastasis, and identification of the most interesting enzymes to target. I will then validate these targets through functional studies in preclinical models and analysis of expression levels in patient tumor samples. This better understanding of the metabolism of TNBC in the bone is essential for the development of new diagnostic tools and therapeutic targets.
Original text from CORDIS.
Participants
- KATHOLIEKE UNIVERSITEIT LEUVEN · LeuvenCoordinatorBelgium
Links
Data: CORDIS, © European Union