Assaf Zaritsky

School of Computer Science, Tel Aviv University, Tel Aviv, Israel

Measuring Collective Tumor Cell Migration

Collective cell migration plays a major role in many essential biological processes. Understanding the molecular and cellular mechanisms of this migration mode is limited despite decades of extensive investigations

A set of quantitative measures, based on live cell imaging is presented, to demonstrate enhanced analyses of collective cell motility in a high throughput manner. The toolbox includes multi-cellular segmentation, motion estimation and tracking, motion in clusters, and measures for cells' individuality, indirect morphology and spatiotemporal motility and visualization.

The subject matter studied is induction of collective tumor cell migration by Hepatocyte Growth Factor / Scatter Factor (HGF/SF) - Met-signaling, master regulators of cell motility in normal and malignant processes. HGF/SF-Met-signaling dramatically alters the morpho-kinetic dynamics of collective migration of breast cancer tumor cells by increasing cells' orientation and cooperation capabilities. Met-inhibition reduces these phenomena.

Exploiting these high-throughput phenotyping capabilities revealed that HGF/SF signaling induced metabolic plasticity of the cells altering from glycolysis to oxidative phosphorylation thus increasing collective cell motility. However a profound inhibition of hexokinase activity significantly reduces it.

Another application was to investigate cells that maintain amoeboid-like motility while traversing in a tissue consisting of epithelial cells, as a simple model for initial metastasis formation. Low concentrations of exogenous YFP- WT-Met, activating and inhibitory forms, were expressed in a monolayer of tumor cells to simulate the phenomenon. Activating Met-variants are generally characterized by cells' amoeboid-like motility; Met-inhibition induces epithelial motility, while HGF/SF-induces increased individuality, a measure for the motility of transfected cells in relation to their vicinity of untreated cells.

The findings reported here are anticipated to shed light on the molecular and cellular alterations that enable metastasis formation in breast cancer and hence to aid in identifying new targets for therapy.

ההרצאה תתקיים ביום ראשון 25.11.2012, בשעה 14:45,

בחדר 315, הבניין הרב תחומי, אוניברסיטת תל אביב