Summary
Communication between different cell types is essential for many biological processes, both in homeostasis and in disease. In tumor initiation, growth and metastasis, cancer cells send and receive chemical and physical cues from their microenvironment. Those cues determine how disease progresses and influence proliferation and invasiveness of malignant cells. Understanding the crosstalk between cancer cells and their immediate environment is crucial for the advance of novel cancer therapies. Thanks to the development of single-cell technologies, we can now sample the complexity and the many functions of the tumor microenvironment. While immune cells are at the forefront of these studies, the mesenchymal fibroblast component is also a highly pertinent and significant player. In this proposal, I will focus on proximal communication between cancer cells and mesenchymal fibroblasts. Using intestinal cancer as a model, I will apply a multimodal approach to investigate the consequences of tissue crosstalk in the early stages of epithelial transformation and the activation of cancer-associated fibroblasts (CAFs). First, I will use tumoral organoid-naive fibroblast co-cultures to study the crosstalk between epithelium and mesenchymal fibroblasts in vitro, and its effect on fibroblasts gene expression pattern (objective 1). Secondly, I will interrogate the response of mesenchymal fibroblasts to epithelial transformation in vivo at single cell depth. I will identify new fibroblasts subpopulations (CAFs), study their origin and transcription factors involved in their activation (objective 2). Finally, I will study the tissue re-organization induced by crypt hyperproliferation using high-resolution confocal imaging and in situ hybridization, to spatially contextualize any changes in gene expression (objective 3). Results from these three objectives will enhance understanding of cellular crosstalk in early stages of cancer and the mechanism of CAFs activation.
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More information & hyperlinks
| Web resources: | https://cordis.europa.eu/project/id/101153729 |
| Start date: | 01-06-2024 |
| End date: | 31-05-2026 |
| Total budget - Public funding: | - 183 600,00 Euro |
Cordis data
Original description
Communication between different cell types is essential for many biological processes, both in homeostasis and in disease. In tumor initiation, growth and metastasis, cancer cells send and receive chemical and physical cues from their microenvironment. Those cues determine how disease progresses and influence proliferation and invasiveness of malignant cells. Understanding the crosstalk between cancer cells and their immediate environment is crucial for the advance of novel cancer therapies. Thanks to the development of single-cell technologies, we can now sample the complexity and the many functions of the tumor microenvironment. While immune cells are at the forefront of these studies, the mesenchymal fibroblast component is also a highly pertinent and significant player. In this proposal, I will focus on proximal communication between cancer cells and mesenchymal fibroblasts. Using intestinal cancer as a model, I will apply a multimodal approach to investigate the consequences of tissue crosstalk in the early stages of epithelial transformation and the activation of cancer-associated fibroblasts (CAFs). First, I will use tumoral organoid-naive fibroblast co-cultures to study the crosstalk between epithelium and mesenchymal fibroblasts in vitro, and its effect on fibroblasts gene expression pattern (objective 1). Secondly, I will interrogate the response of mesenchymal fibroblasts to epithelial transformation in vivo at single cell depth. I will identify new fibroblasts subpopulations (CAFs), study their origin and transcription factors involved in their activation (objective 2). Finally, I will study the tissue re-organization induced by crypt hyperproliferation using high-resolution confocal imaging and in situ hybridization, to spatially contextualize any changes in gene expression (objective 3). Results from these three objectives will enhance understanding of cellular crosstalk in early stages of cancer and the mechanism of CAFs activation.Status
SIGNEDCall topic
HORIZON-MSCA-2023-PF-01-01Update Date
21-11-2024
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