Intravital lineage tracing of (cancer) stem cells in genetic mouse models


Ontology type: schema:MonetaryGrant     


Grant Info

YEARS

2013-2016

FUNDING AMOUNT

192823 GBP

ABSTRACT

For the initiation and progression of a tumor, multiple genetic hits have to occur in a single cell. Adult stem cells and cancer stem cells are thought to be a long-lived static population of cells and therefore the mutation-acquiring cells; however this idea has recently been disputed. Instead, it has been suggested that stem cells may compete and drift toward clonality, and that stem cells may even be replaced by differentiated cells that dedifferentiate into new stem cells. Obviously, the existence of (cancer) stem cell plasticity and competition and the mechanisms behind it are of utmost importance to understand the initiation and progression of tumors. To study this, we have developed unique intravital lineage tracing techniques to directly visualize the dynamic behavior of stem cells and their progeny in living mice for several weeks. In contrast to static images in standard lineage tracing experiments, we are able to visualize the stem cells competition and dedifferentiation events in real time. Several genetic mouse models developed to fluorescently lineage trace (cancer) stem cells in the healthy and tumorigenic intestinal and breast tissue will be intravitally imaged to study 1) whether (cancer) stem cells display clonal outgrowth, 2) whether dedifferentiation occurs, 3) the occurrence of symmetric and asymmetric (cancer) stem cell divisions and the location of these events with respect to other (cancer) stem cells, 4) whether (cancer) stem cells are static or mobile, 5) whether the number of (cancer) stem cells is fixed or flexible, and 6) the importance of (cancer) stem cell plasticity during metastatic outgrowth. Thus, our unique intravital lineage tracing tools allow us to study the dynamic behavior of differentiated and (cancer) stem cells and their role in healthy and tumorigenic colorectal and mammary tissue. More... »

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