Identifying site-specific metastasis genes and functions
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 unbiased and comprehensive biological scrutiny. I...
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| Veröffentlicht in: | Cold Spring Harbor Symposia on Quantitative Biology 2005, Vol.70, p.149-158 |
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| container_title | Cold Spring Harbor Symposia on Quantitative Biology |
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| creator | Gupta, G P Minn, A J Kang, Y Siegel, P M Serganova, I Cordón-Cardo, C Olshen, A B Gerald, W L Massagué, J |
| description | 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 unbiased and comprehensive biological scrutiny. In recent years, we have utilized a xenograft model of breast cancer metastasis to discover genes that mediate organ-specific patterns of metastatic colonization. Examination of transcriptomic data from cohorts of 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 of poor prognosis. These genes fulfill dual functions-enhanced primary tumorigenicity and augmented organ-specific metastatic activity. Other metastasis genes fulfill functions specialized for the microenvironment of the metastatic site and are consequently not selected for in primary tumors. These findings improve our understanding of metastatic progression, facilitate the interpretation of primary tumor gene expression data, and open several important possibilities for future clinical application. |
| doi_str_mv | 10.1101/sqb.2005.70.018 |
| format | Article |
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Understanding the biological underpinnings of this complex process is of extreme clinical relevance and requires unbiased and comprehensive biological scrutiny. In recent years, we have utilized a xenograft model of breast cancer metastasis to discover genes that mediate organ-specific patterns of metastatic colonization. Examination of transcriptomic data from cohorts of 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 of poor prognosis. These genes fulfill dual functions-enhanced primary tumorigenicity and augmented organ-specific metastatic activity. Other metastasis genes fulfill functions specialized for the microenvironment of the metastatic site and are consequently not selected for in primary tumors. These findings improve our understanding of metastatic progression, facilitate the interpretation of primary tumor gene expression data, and open several important possibilities for future clinical application.</description><subject>Animals</subject><subject>Bone Neoplasms - genetics</subject><subject>Bone Neoplasms - pathology</subject><subject>Bone Neoplasms - secondary</subject><subject>Breast Neoplasms - genetics</subject><subject>Breast Neoplasms - pathology</subject><subject>Cell Line, Tumor</subject><subject>Female</subject><subject>Gene Expression Profiling</subject><subject>Humans</subject><subject>Lung Neoplasms - genetics</subject><subject>Lung Neoplasms - pathology</subject><subject>Lung Neoplasms - secondary</subject><subject>Mice</subject><subject>Neoplasm Metastasis - genetics</subject><subject>Neoplasm Metastasis - pathology</subject><subject>Neoplasm Transplantation</subject><subject>Oncogenes</subject><subject>Organ Specificity</subject><subject>Prognosis</subject><subject>Transplantation, Heterologous</subject><issn>0091-7451</issn><issn>1943-4456</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2005</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpFkDtrwzAUhUVpadK0c7fiqZsdXes9ltBHINClnYUiXwWVWE4se8i_r0sChQNn-c4ZPkIegVYAFJb5uK1qSkWlaEVBX5E5GM5KzoW8JnNKDZSKC5iRu5x_KK0NCH5LZiC1NIrrOdHrBtMQwymmXZHjgGU-oI8h-qLFweUpMRc7TJgLl5oijMkPsUv5ntwEt8_4cOkF-X57_Vp9lJvP9_XqZVN6xuRQbl3tPENECIY642uhuOdGA1PBIPcShQGj0QhdO1EzBRw4pbqRjdRBCbYgz-ffQ98dR8yDbWP2uN-7hN2YraKgJHAzgcsz6Psu5x6DPfSxdf3JArV_suwky_7JmjZ2kjUtni7X47bF5p-_2GG_NsZkww</recordid><startdate>2005</startdate><enddate>2005</enddate><creator>Gupta, G P</creator><creator>Minn, A J</creator><creator>Kang, Y</creator><creator>Siegel, P M</creator><creator>Serganova, I</creator><creator>Cordón-Cardo, C</creator><creator>Olshen, A B</creator><creator>Gerald, W L</creator><creator>Massagué, J</creator><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>2005</creationdate><title>Identifying site-specific metastasis genes and functions</title><author>Gupta, G P ; Minn, A J ; Kang, Y ; Siegel, P M ; Serganova, I ; Cordón-Cardo, C ; Olshen, A B ; Gerald, W L ; Massagué, J</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c336t-ba2ac3eee1f90a9c2574c498137f9e4c6e59198e9582a52371414008d6d68f753</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2005</creationdate><topic>Animals</topic><topic>Bone Neoplasms - genetics</topic><topic>Bone Neoplasms - pathology</topic><topic>Bone Neoplasms - secondary</topic><topic>Breast Neoplasms - genetics</topic><topic>Breast Neoplasms - pathology</topic><topic>Cell Line, Tumor</topic><topic>Female</topic><topic>Gene Expression Profiling</topic><topic>Humans</topic><topic>Lung Neoplasms - genetics</topic><topic>Lung Neoplasms - pathology</topic><topic>Lung Neoplasms - secondary</topic><topic>Mice</topic><topic>Neoplasm Metastasis - genetics</topic><topic>Neoplasm Metastasis - pathology</topic><topic>Neoplasm Transplantation</topic><topic>Oncogenes</topic><topic>Organ Specificity</topic><topic>Prognosis</topic><topic>Transplantation, Heterologous</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Gupta, G P</creatorcontrib><creatorcontrib>Minn, A J</creatorcontrib><creatorcontrib>Kang, Y</creatorcontrib><creatorcontrib>Siegel, P M</creatorcontrib><creatorcontrib>Serganova, I</creatorcontrib><creatorcontrib>Cordón-Cardo, C</creatorcontrib><creatorcontrib>Olshen, A B</creatorcontrib><creatorcontrib>Gerald, W L</creatorcontrib><creatorcontrib>Massagué, J</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Cold Spring Harbor Symposia on Quantitative Biology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Gupta, G P</au><au>Minn, A J</au><au>Kang, Y</au><au>Siegel, P M</au><au>Serganova, I</au><au>Cordón-Cardo, C</au><au>Olshen, A B</au><au>Gerald, W L</au><au>Massagué, J</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Identifying site-specific metastasis genes and functions</atitle><jtitle>Cold Spring Harbor Symposia on Quantitative Biology</jtitle><addtitle>Cold Spring Harb Symp Quant Biol</addtitle><date>2005</date><risdate>2005</risdate><volume>70</volume><spage>149</spage><epage>158</epage><pages>149-158</pages><issn>0091-7451</issn><eissn>1943-4456</eissn><abstract>Metastasis is a multistep and multifunctional biological cascade that is the final and most life-threatening stage of cancer progression. 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| source | MEDLINE; EZB-FREE-00999 freely available EZB journals |
| subjects | Animals Bone Neoplasms - genetics Bone Neoplasms - pathology Bone Neoplasms - secondary Breast Neoplasms - genetics Breast Neoplasms - pathology Cell Line, Tumor Female Gene Expression Profiling Humans Lung Neoplasms - genetics Lung Neoplasms - pathology Lung Neoplasms - secondary Mice Neoplasm Metastasis - genetics Neoplasm Metastasis - pathology Neoplasm Transplantation Oncogenes Organ Specificity Prognosis Transplantation, Heterologous |
| title | Identifying site-specific metastasis genes and functions |
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