Collective invasion Group
This group belongs to the UMR 1279 Tumor Cells Dynamics.
Metastases formation is the current clinical challenge for cancer patient treatment. Invasion, the locomotion of tumour cells into tissues, is the first and last step in the metastatic cascade. The first step, when the carcinoma crosses the basal lamina to enter the peri-tumour microenvironment, and the last step, after translocation to distant organ, when the tumour cells penetrate into tissues at secondary site. Invasion has been extensively studied in the context of the epithelial-to-mesenchymal transition (EMT), a vast transcriptional program mediating the dissemination of individual single cells that have lost cell-cell junctions and epithelial features. However, numerous histological studies demonstrate that CRC predominantly invade as cohesive tumour cell cohorts maintaining cell-cell junctions and epithelial architecture. This second mode of invasion, recently defined as collective invasion, preponderantly underlies the dissemination of most carcinomas, remains mostly under-investigated.
Our research focuses on collective invasion of colorectal carcinoma (CRC), the second leading cause of cancer related death. We aim at identifying the signalling pathways regulating collective invasion; the factors dictating single cell or collective invasion mode (and whether tumour cell can alternate between these strategies) and the respective activities of leaders (protrusive cells at the front of the group) and followers (cells at the back). We use molecular and cell biology approaches, combining spinning disc confocal microscopy and 3D organotypic cultures along two main research axes:
- We use versatile models, such as cysts (derived from cell lines) or organoïds/tumouroïds (generated from tumours) in order to decipher the cellular and molecular mechanisms underlying collective invasion.
- As a collaborative work with clinicians, we investigate tumour dissemination toward the peritoneal cavity (peritoneal carcinomatosis, PC), the second metastatic site in CRC patients. We work on fresh and fixed patients’ samples in order to understand the molecular bases of PC and identify clinical tools to improve patients’ care.