Identifying Site-specific Metastasis Genes and Functions
- G.P. GUPTA*,
- A.J. MINN*,§,
- Y. KANG*,**,
- P.M. SIEGEL*,#,
- I. SERGANOVA†,
- C. CORDÓN-CARDO‡,
- A.B. OLSHEN¶,*,
- W.L. GERALD‡, and
- J. MASSAGUÉ
- *Cancer Biology and Genetics Program and Howard Hughes Medical Institute, Memorial Sloan-Kettering Cancer Center, New York, New York 10021
- †Department of Neurology, Memorial Sloan-Kettering Cancer Center, New York, New York 10021
- ‡Department of Pathology, Memorial Sloan-Kettering Cancer Center, New York, New York 10021
- ¶Department of Biostatistics, Memorial Sloan-Kettering Cancer Center, New York, New York 10021
- §Present addresses: Department of Radiation Oncology, University of Chicago, Chicago, Illinois 60637, McGill University, Montreal, Quebec, Canada H34 1A4.
- **Present addresses: Department of Molecular Biology, Princeton University, Princeton, New Jersey 08544, McGill University, Montreal, Quebec, Canada H34 1A4.
- #Present addresses: Departments of Medicine and Biochemistry, McGill University, Montreal, Quebec, Canada H34 1A4.
Abstract
Metastasis is a multistep and multifunctional biological cascade that is the final and most life-threatening stage of cancer progression.Understanding the biological underpinnings of this complex process is of extreme clinical relevance and requires unbiasedand comprehensive biological scrutiny. In recent years, we have utilized a xenograft model of breast cancer metastasisto discover genes that mediate organ-specific patterns of metastatic colonization. Examination of transcriptomic data from cohortsof primary breast cancers revealed a subset of site-specific metastasis genes that are selected for early in tumor progression.High expression of these genes predicts the propensity for lung metastasis independently of several classic markers ofpoor prognosis. These genes fulfill dual functions—enhanced primary tumorigenicity and augmented organ-specific metastaticactivity. Other metastasis genes fulfill functions specialized for the microenvironment of the metastatic site and are consequentlynot selected for in primary tumors. These findings improve our understanding of metastatic progression, facilitate theinterpretation of primary tumor gene expression data, and open several important possibilities for future clinical application.
Footnotes
- Copyright 2005, Cold Spring Harbor Laboratory Press
