Gender	Female
E-mail	liliana.ossowski@mssm.edu
Education and Training	PhD, Weizmann Institute
	MSc, Hadassah Medical School
	Post-doctoral Training, Laboratory of Chemical Biology, Rockefeller University

Education and Training	PhD, Weizmann Institute
	MSc, Hadassah Medical School
	Post-doctoral Training, Laboratory of Chemical Biology, Rockefeller University

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.

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.

Aguirre-Ghiso J, Kovalski K, Ossowski L. Tumor dormancy induced by down regulation of urokinase receptor in human carcinoma involves integrin and MAPK signaling. J Cell Biol 1999; 147: 89-103.

Ossowski L, Aguirre-Ghiso JA. Urokinase receptor and integrin partnership; coordination of signaling for cell adhesion, migration and growth. Curr Op Cell Biology 2000; 12: 613-620.

Aguirre-Ghiso J, Liu D, Mignatti A, Kovalski K, Ossowski L. Urokinase receptor and fibronectin regulate the ERK^MAPK to p38^MAPK activity ratios and determine carcinoma cell proliferation or dormancy in vivo. Mol Biol Cell 2001; 12: 863-879.

Wang LG, Ossowski L, Ferrari A. Overexpression of androgen receptor linked to p21^WAF/CIP1 silencing may be responsible for androgen independence and resistance to apoptosis of a prostate cancer cell line. Cencer Res 2001; 61: 7544-7551.

Aguirre-Ghiso J, Liu D, Mignatti A, Kovalski K, Ossowski L. Urokinase receptor and fibronectin regulate the ERKMAPK to p38MAPK activity ratios and determine carcinoma cell proliferation or dormancy in vivo. Mol Biol Cell 2001; 12: 863-879.

Liu D, Aguirre-Ghiso J, Estrada Y, Ossowski L. Urokinase receptor induced ligand-independent EGFR signaling. Cancer Cell 2002; 1: 445-457.

Liu D, Aguirre-Ghiso J, Estrada Y, Ossowski L. Urokinase receptor induced ligand-independent EGFR signaling. Cancer Cell 2002; 1: 445-457.

Aguirre-Ghiso JA, Estarda Y, Liu D, Ossowski L. ERK (MAPK) activity as a determinant of tumor growth and dormancy; regulation by p38(SAPK). Cancer Res 2003; 63: 1684-1695.

Aguirre-Ghiso JA, Estrada Y, Lu D, Ossowski L. ERK(MAPK) activity as a determinant of tumor growth and dormancy; regulation by p38(SAPK). Cancer Res 2003; 63: 16845-16895.

Aguirre-Ghiso JA, Ossowski L, Rosenbaum S. Green fluorescent protein tagging of extracellular signal-regulated kinase and p38 pathways reveals novel dynamics of pathway activation during primary and metastatic growth. Cancer Res. 2004; 64: 7336-7345.

Wang LG, Ossowski L, Ferrari A. Androgen Receptor Level Controlled by a Suppressor Complex Lost in an Androgen Independent Prostate Cancer Cell Line. Oncogene 2004; 23: 5175-5184.

Franco P, Vocca I, Alfano D, Cito L, Longanessi-Cattani I, Grieco P, Ossowski L, Stoppelli MP. Activation of urokinase receptor by a novel interaction between the connecting peptide region of urokinase and {alpha}v{beta}5 integrin. J Cell Sci 2006; 119: 3424-3434.

Chaurasia P, Aguirre-Ghiso JA, Liang OD, Gardsvoll H, Ploug M, Ossowski L. A region in urokinase plasminogen receptor domain III controlling a functional association with alpha5beta1 integrin and tumor growth. J Biol Chem 2006; 281: 14852-14863.

Mazzieri R, D'Alessio S, Kenmoe RK, Ossowski L, Blasi F. An uncleavable uPAR mutant allows dissection of signaling pathways in uPA-dependent cell migration. Mol Biol Cell 2006; 17: 367-378.