Project description
Insight into the role of the cancer stem cell niche
Tissue-specific stem cells are undifferentiated cells that have the capacity to self-renew and generate multiple types of cells within the tissue. Stem cell maintenance and function depend on the stem cell niche, a specialised location within tissues. The EU-funded IntratumoralNiche project is working under the hypothesis that a similar niche exists in tumours and supports cancer stem cells, tumour growth and metastasis formation. Researchers aim to dissect the signalling cues of the intratumoural niche using patient-derived organoid cultures and animal models of colorectal cancer. Results will unveil the role of the different components of the niche in tumour progression, potentially identifying novel therapeutic targets.
Objective
Purpose: Cells in a tumor are highly heterogeneous. The role and consequence of having multiple cell types within a cancer is mostly centered towards the function of cancer stem cells (CSCs) since they are the driving forces of tumor growth. However, the exact signaling cues that support CSC function remain to be understood. For instance, what are the roles of immediate descendant tumor cells in relation to CSC support? Do colorectal tumors make their own niche?
Preliminary data: To study communication between different cell types (heterocellular signaling) in human colorectal cancers (CRCs), my lab developed movieSTAR technology to mark CSCs in patient-derived CRC organoids (PDOs) for high-resolution live imaging of their dynamics and behavior. Although niche factor dependency decreases along the adenoma-carcinoma transition, we identified a strong interdependency between CSCs and other tumor cells in colorectal PDOs of malignant nature.
Hypothesis: We hypothesize a continuous existence of an intratumoral stem cell niche that remains essential for tumor growth and metastasis formation. Which types of heterocellular signaling support CSC function, especially at malignant stages, is unknown.
Approach: This project aims to define heterocellular signaling between CSCs and intratumoral niche cells. Therefore, I) we will combine our expertise in human organoid technology for in-depth characterization of the nature of heterocellular communication within the intratumoral niche, II) high-resolution live imaging of PDOs to interrogate heterogeneity of signaling activities at cellular resolution and in real-time, as well as III) in vivo mouse models for validation and further studies of essential intratumoral signaling pathways.
Innovation: Our integrative use of novel approaches will provide comprehensive insight into intratumoral niche function during tumorigenesis, establishing novel technologies for future cancer research and new concepts to improve cancer therapy.
Fields of science
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Topic(s)
Funding Scheme
ERC-STG - Starting GrantHost institution
3584 CX Utrecht
Netherlands