Abstract
Cancer metastasis is a complex, dynamic process that begins with dissemination of cells from the primary tumor and culminates in the formation of clinically detectable, overt metastases at one or more discontinuous secondary sites. Evidence from in vivo video microscopy as well as PCR and immunohistochemical studies suggest that cancer cell dissemination is an early event in tumor progression and that cells may persist in a potentially dormant state for a prolonged period. Similarly, the mechanisms by which these disseminated cells initiate growth and complete the process of metastatic colonization remain largely unknown. Understanding signal transduction pathways regulating this final step of metastasis is therefore critical for successful clinical management. While genetic mutations or epigenetic changes may be required for a cell or group of cells to separate and survive distant from the primary tumor, the microenvironment within secondary tissues plays a substantial role in influencing whether disseminated cells survive and proliferate. Our work is focused on using metastasis suppressor proteins to gain insight into why the majority of disseminated cells, which should be fully malignant, do not proliferate immediately at secondary sites. The translational goal of this work is to identify targets for inhibiting metastatic growth and prolonging disease-free survival.
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Acknowledgements
We express our appreciation to Dr. Russell Szmulewitz for his critical and thoughtful reading of our manuscript. We thank Dr. Arieh Shalhav, Dr. Charles Brendler and the University of Chicago Section of Urology for their strong and unwavering support our metastasis suppressor protein studies. This work supported by The University of Chicago RESCUE Fund (CWR-S); DOD Ovarian Cancer Research Grant DAMD17-03-1-0169 (JH, DY), Grant RO1 CA 89569 (CWR-S, JH), DOD Ovarian Cancer Research Grant W81XWH-06-1-0041 (CWR-S), Gynecologic Cancer Foundation/Ann Schreiber Ovarian Cancer Research Grant (JH, CWR-S), support from the Department of Pathology (TL) and Graduate Training in Growth and Development T32 HD07009 (JLT).
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Taylor, J., Hickson, J., Lotan, T. et al. Using metastasis suppressor proteins to dissect interactions among cancer cells and their microenvironment. Cancer Metastasis Rev 27, 67–73 (2008). https://doi.org/10.1007/s10555-007-9106-7
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DOI: https://doi.org/10.1007/s10555-007-9106-7