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.