Theresa Vincent – Molecular cancer and stem cell therapeutics

Ninety percent of all cancer deaths arise from tumour metastasis. Our research focuses on the process when tumour cells migrate from the tumour to blood and lymph vessels where they can spread to other parts of the body. Our goal is a better understanding of the complex mechanisms behind metastasis and that our results in the long-term can be applied in the clinic.

The process of metastasis depends on the delamination and spread of tumour cells. Only a minority of the tumour cells, i.e. tumour-initiating cells also referred to as cancer stem cells (CSCs), are capable of successfully seeding a distant site. The CSC hypothesis proposes that only a subset of tumour cells have the ability to self-renew and are thus responsible for driving tumorigenesis, making them ideal targets for cancer intervention.

Cancer stem cells are formed during the metastatic process

Our research group focuses on the early steps of the metastatic process, i.e. migration and invasion of the tumour cells into circulation through a process known as epithelial to mesenchymal transition (EMT) and the mechanisms controlling this process. Recent discoveries have provided the compelling evidence that during the process of EMT cells are converted into CSCs.

The fact that cells acquire stem-like traits during the process of migration, invasion and intravasation i.e. EMT, opens up a new and exciting area of research – merging stem cell biology and cancer biology. It also highlights the need for further EMT research within the cancer field.
 

Evidence of epithelial to mesenchymal transition in invasive human breast cancer. Loss of tight junctional proteins (CAR protein, lilac) is associated with nuclear co-expression of Smad4 (green) and Snail (red) and invasion into the stroma (black).  Cell Cycle 2010 Jun;9(12):2363-74.

Identification of cellular events that affect metastasis

Our main interest is to gain a better understanding of cellular changes that induce EMT and conversion to CSCs. We are studying the role of cell signalling such as TGFb and Wnt and its role in migration and spread of cancers including breast and glioma using both in vitro and in vivo models. Of particular interest is the emerging area of epigenetics and metabolism and its importance for EMT.

Another interest is in mechanobiology i.e. how mechanical pressure within the tumour’s micro/nanoenvironment will affect metastasis. Our long-term goal is that these studies will provide significant insight into the complex mechanism of tumour spread and metastasis and ultimately allow for our research to advance into a clinical setting.

The importance of collaboration

Currently, we have several ongoing national and international research projects within these areas and our laboratory places a special focus on international collaborative efforts. It is our ambition to create a unique laboratory and educational environment that is not limited by departmental or national barriers but only by our scientific education, curiosity and ambition.