Research Summary
Understand the biology of ovarian cancer invasion and metastasis and identify novel targets for treatment
My laboratory is dedicated to improving our understanding of the biology of ovarian cancer growth and dissemination, and to exploring the use of novel drugs for its treatment. Ovarian cancer has the highest mortality rate of all gynecologic tumors and is the 5th leading cause of cancer death among U.S. women. It is often diagnosed at a late stage, when tumor cells are disseminated within the peritoneal cavity. After malignant transformation of ovarian surface epithelial cells and growth within the ovary, tumor cells detach from the ovary and attach to the peritoneum where they grow as nodules but rarely leave the peritoneal cavity. Despite aggressive treatment more than two thirds of all patients succumb to their disease within 5 years.
Several classes of extracellular matrix degrading proteases have been shown to play an important role in tumor invasion and metastasis. We have chosen to focus on two of these, the plasminogen activator plasmin system and the matrix metalloproteases. We are now attempting to understand the roles they play during the malignant transformation, invasion, dissemination, and recurrence of human ovarian cancer. Since many proteases are regulated transcriptionally, our focus is on the regulation of proteases in ovarian cancer cells and their interaction with adhesion molecules of the integrin class. We have previously shown that one protease receptor, the urokinase receptor, downregulates the beta3-integrin receptor and, therefore, effects adhesion. Currently, we are investigating how protease and adhesion receptors regulate each other, and how this activity effects tumor cell attachment and proteolysis in vitro and in vivo. In addition, the laboratory is exploring the role of HGF and c-Met in breast and ovarian cancer to determine if c-Met is a therapeutic target. We have characterized HGF and c-Met expression, (Cancer Research, in press) and are now investigating the effect, on tumor growth and the dissemination of ovarian cancer cells, of inhibiting c-Met with small molecule inhibitors and siRNA. Last, we have developed a 3D model of ovarian cancer metastasis to the omentum.
We previously used ovarian cancer cell lines and mouse models of ovarian cancer (xenograft, genetic) in our research, but we now intend to test our hypothesis in human ovarian cancer tissue. For this purpose, we have cooperated closely with Dr. Montag, a Gynecologic Pathologist at the University of Chicago, to assemble a large ovarian tumor bank with annotated patient data. Ultimately, we hope to realize the major goal of the laboratory; to translate our findings and understanding of ovarian cancer tumor biology into novel therapeutic treatments for ovarian cancer. Our research is funded by the NIH, the Ovarian Cancer Research Foundation, and the Gynecologic Cancer Foundation.
Ernst Lengyel
April 2008
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Principal Investigator
Ernst Lengyel, MD, PhD
elengyel@uchicago.edu
Assistant Professor
The University of Chicago
Section of Gynecologic Oncology, MC 2050
929 E. 57th St.
Rms W106 (office) and W107 (lab)
Chicago, Illinois 60637, USA
Geri Cooper, Academic Assistant
Committee on Cancer Biology Web page
Songuel Dogan, PhD
Postdoctoral Fellow
sdogan@babies.bsd.uchicago.edu
Swayamjot Kaur, PhD
skaur@babies.bsd..uchicago.edu
Hilary Kenny, PhD
hkenny@babies.bsd.uchicago.edu
Sujatha Jagadeeswaran, MS
sjagadee@babies.bsd.uchicago.edu
Marcin Mackowski
Exchange Student
mmackowski@babies.bsd.uchicago.edu
Postdoctoral Fellow
amitra@babies.bsd.uchicago.edu
General OBGYN
iris.romero@
Student
International Journal of Cancer
displays a picture of the 3D omental
metastasis model created by the Lengyel Lab
click here to see it
Press Releases
July, 2007
March, 2008
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