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JNCI Journal of the National Cancer Institute 2000 92(21):1717-1730; doi:10.1093/jnci/92.21.1717
© 2000 by Oxford University Press
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Journal of the National Cancer Institute, Vol. 92, No. 21, 1717-1730, November 1, 2000
© 2000 Oxford University Press


REVIEW

Metastasis-Suppressor Genes: a Review and Perspective on an Emerging Field

Barbara A. Yoshida, Mitchell M. Sokoloff, Danny R. Welch, Carrie W. Rinker-Schaeffer

Affiliations of authors: B. A. Yoshida, M. M. Sokoloff, C. W. Rinker-Schaeffer, Section of Urology and Genitourinary Oncology Research Program of the University of Chicago, IL; D. R. Welch, The Jake Gittlen Cancer Research Institute, The Pennsylvania State University College of Medicine, Hershey.

Correspondence to: Carrie W. Rinker-Schaeffer, Ph.D., Section of Urology, Department of Surgery MC6038, The University of Chicago, 5831 S. Maryland Ave., Chicago, IL 60637 (e-mail: crinker{at}surgery.bsd.uchicago.edu).

Metastasis is the most lethal attribute of a cancer. There is a critical need for markers that will distinguish accurately those histologic lesions and disseminated cells with a high probability of causing clinically important metastatic disease from those that will remain indolent. While the development of new diagnostic markers of metastasis was the initial motivation for many studies, the biologic approach used to identify metastasis-suppressor genes has provided surprising insights into the in vivo mechanisms regulating the formation of metastases. This review and perspective describes the evolving view of the mechanisms that regulate metastasis and the importance of metastasis-suppressor genes in this process. The known metastasis-suppressor proteins or genes and the microcell-mediated chromosomal transfer strategy used to identify many of them are reviewed. New evidence for the role of these metastasis-suppressor proteins or genes in regulating the growth of disseminated cancer cells at the secondary site, the potential for the identification of novel therapeutic targets, and the multidisciplinary approach needed to translate this information into clinical tools for the treatment of metastatic disease are discussed.



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