"Studying the mechanisms of the intravascular adhesion and extravasation of Pancreatic cancer cells."

"Studying the mechanisms of the intravascular adhesion and extravasation of Pancreatic cancer cells."

Solid tumor progression is a dynamic succession of events, happening in different spaces and times in the body, ultimately leading to the formation of life-threatening metastases. To colonize distant organs, cancer cells are exploiting the circulatory networks as natural paths before stopping in small vessels and crossing the endothelial barrier. During transportation, the cells are subjected to harsh physico-chimical parameters and to different cell types compared to their primary tumor of origins. This is a critical situation for them, attested by the massive difference between circulating tumor cell (CTC) counts in patients, and the actual metastatic dissemination. Nevertheless, some of them survive by developing a series of survival, adhesion and migration strategies. All of this remain poorly understood.

My research focuses on the steps of adhesion and extravasation (crossing of the vessel border) of pancreatic ductal adenocarcinoma (PDAC) cell lines. My main objectives are to decipher the mechanisms allowing the cells to break the endothelial barrier, in an attempt to identify key factors and actors during the process. I work with microfluidic models to better reproduce the physiologic conditions of perfused vessels, zebrafish embryos which are transparent and very rapidly develop a complex vascular system, allowing unprecedent live imaging resolution, and mice models. All three are coupled with quantitative and high-resolution imaging and to single cell characterization approaches (scRNAseq and mass cytometry).

My ongoing results support the idea that heterogeneity of cancer cells, even among laboratory cell lines, is driving different adhesion/extravasation modes. My talk will focus on two unpublished aspects: 1. Our extra effort to better understand the bio-physicals context during the steps of adhesion and extravasation, using Super Resolution microscopy and AFM. 2. The live and fixed microscopic dissection of the transmigration mechanisms of several PDAC cell lines. Understanding the drivers of such different behavior is necessary to propose novel clinical avenue.

Previous work:
Follain et al. Fluids and their mechanics in tumour transit: shaping metastasis. NRC 2020
Follain et al. Hemodynamic forces tune the arrest, adhesion and extravasation of circulating tumor cells. Dev Cell. 2018