Project description
Insight into crossing tissue borders in cancer metastasis
Epithelial-to-mesenchymal transition (EMT) is a biological process where epithelial cells, typically characterised by tight cell-cell adhesion, lose their epithelial traits and acquire mesenchymal characteristics. This transition is crucial in various physiological and pathological processes, including cancer metastasis. The ERC-funded BorderControl project aims to investigate how cancer cells interact with endothelial cells to overcome physiological barriers and spread to other tissues. Using advanced techniques, researchers will uncover the molecular signals that regulate the EMT transition. The identification of novel biomarkers and therapeutic targets is expected to lead to clinical applications and improve cancer treatment outcomes.
Objective
During dissemination, cancer cells must face and overcome several physiological borders, including the immediate stroma for local invasion and the endothelium for long-distance metastasis. At these critical junctures, cell plasticity between epithelial (E) and mesenchymal (M) states could determine metastasis potential. Based on our preliminary data, ideally-positioned cues emanating from the normal stroma contain the tumour in situ. Once this first border is breached, rare cancer cell-endothelial interactions trigger further dissemination through the vascular border. Moreover, cancer cell plasticity is vital throughout this process, enabling optimal response to distinct border microenvironments.
In BorderControl, we will build on our cutting-edge cell biology expertise and close collaboration with clinicians to define the molecular signals underlying these border crossings and gain unprecedented information on how cancer cells overwhelm these natural defences. Starting with patient tissues, we will spatially profile the tumour-stroma border to identify receptor-ligand pairs that regulate invasion. We will use microfluidics to image, catch and profile cancer cell crossings at endothelial hotspots and determine key molecular regulators of the process in endothelial and cancer cells. Building on our novel discovery of endosomally regulated E-M cell states, we will test how E-M transitions impact border-breaching potential. These novel concepts will be investigated with interdisciplinary methods (scRNAseq, synthetic biology, colour barcoded HTS) and our new technologies (dynamically tuneable multicell-type migration and invasion imaging platforms) to determine the specific interactions/mechanisms regulating border crossings. Finally, we will take the molecular level discoveries from the cancer-limiting borders back to the patients, assessing clinical relevance using designer TMAs, and expect to uncover novel biomarkers and therapeutically actionable targets.
Fields of science (EuroSciVoc)
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques.
- natural sciencesphysical sciencesclassical mechanicsfluid mechanicsmicrofluidics
- natural sciencesbiological sciencescell biology
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Keywords
Programme(s)
- HORIZON.1.1 - European Research Council (ERC) Main Programme
Topic(s)
Funding Scheme
HORIZON-ERC - HORIZON ERC GrantsHost institution
20014 Turku
Finland