Liliana Ossowski, PhD
- PROFESSOR EMERITUS | Medicine
- PROFESSOR EMERITUS | Oncological Sciences
MSc, Hadassah Medical School
PhD, Weizmann Institute
Laboratory of Chemical Biology, Rockefeller University
My laboratory focuses on the properties of cancer cells that distinguish them from normal cells and which allow them to spread (metastasize) in the host. The long-term goal of my research is to identify interactions and functions of cancer cells amenable to inhibition so that targeted cancer therapy can be developed. It is well established that in order to spread, cancer cells have to degrade biological barriers such as basement memrance and extracellular matrix. We have established that a serine protease, which localizes this enzyme activity of urokinase blocks metastasis. We are now studying the receptor trying to determine the steps in metastatic spread which are dependent on surface proteolysis. We have discovered that reduction of the receptor expression by antisense techniques causes cancer cells to enter a state of dormacy (lack of in vivo proliferation). We have determined that through its interaction with an integrin alpha 5 beta1, the urokinase receptor induces activation of MAPkinase-ERK pathway, allowing tumor cells growth in vivo. This is an exciting finding since it provides a new approach to induce arrest of existing micrometastases.
My laboratory works on the concept of cancer dormancy. Observations in cancer patients indicate that cancer cells, which separate from the primary tumor and settle in distant organs, can either immediately resume growth, forming life-threatening metastases, or remain undetected, dormant and harmless to the patient, for prolonged period of time. We developed a cancer model, which allows us to study the molecular interactions that lead to induction of dormancy. Using this model it was possible to show that by disrupting an interaction between two cell surface receptors, urokinase receptor and an integrin, proliferative signal to ERK is blocked and a highly malignant tumor can be plunged into dormancy. This interaction is strictly dependent on high level of urokinase receptor, a property of many malignant tumors, thus making the site of intervention cancer specific. We identified the sequence on the urokinase receptor to which the integrin binds and used it to dock a chemical library of small compounds. One compound possessing the required activity has been identified. The ultimate goal is to develop it into a non-toxic drug that will prevent micro-metastatic disease from progressing to overt metastases.