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Journal of Oncology
Volume 2010, Article ID 286925, 7 pages
http://dx.doi.org/10.1155/2010/286925
Review Article

Disrupting Ovarian Cancer Metastatic Colonization: Insights from Metastasis Suppressor Studies

1Section of Urology, Department of Surgery, The University of Chicago, Chicago, IL 60637, USA
2Committee on Cancer Biology, The University of Chicago, Chicago, IL 60637, USA
3Urology Research, The Departments of Surgery, Obstetrics and Gynecology, and Medicine, The University of Chicago, Chicago, IL 60637, USA

Received 5 August 2009; Accepted 6 December 2009

Academic Editor: Maurie M. Markman

Copyright © 2010 Shaheena Khan et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Ovarian cancer affects approximately 25,000 women in the United States each year and remains one of the most lethal female malignancies. A standard approach to therapy is surgical cytoreduction, after which the remaining microscopic residual disease is treated with chemotherapy. The vast majority of patients have disease recurrence, underscoring the crucial need for approaches to control the regrowth, or colonization, of tissues after local treatment. Improved therapies require mechanistic information about the process of metastatic colonization, the final step in metastasis, in which cancer cells undergo progressive growth at secondary sites. Studies of metastasis suppressors are providing insights into events controlling metastatic colonization. This paper reviews our laboratory's approach to the identification, characterization, and functional testing of the JNKK1/MKK4 metastasis suppressor in ovarian cancer metastatic colonization. Specifically, we demonstrate that interaction of ovarian caner cells with the omental microenvironment activates JNKK1/MKK4 resulting in decreased proliferation without affecting apoptosis. The potential role of the omental microenvironment, specifically milky spot structures, is also described. It is our goal to provide this work as a usable paradigm that will enable others to study metastasis suppressors in clinical and experimental ovarian cancer metastases.