Comparative analysis of gene regulatory networks of highly metastatic breast cancer cells established by orthotopic transplantation and intra-circulation injection

Jun Nakayama, Emi Ito, Jiro Fujimoto, Shinya Watanabe, Kentaro Senba

    Research output: Contribution to journalArticle

    Abstract

    Metastasis signature genes in breast cancer have been studied comparing transcriptomic profiles of highly metastatic cancer cell lines established by intra-circulation injection with that of their parental cell line. However, this method is not suitable to analyze the initial steps of metastasis including invasion into local tissues and the circulatory system. To characterize the molecular mechanisms of early metastasis, we established highly metastatic MDA-MB-231 cell lines that metastasized to lung by the two animal transplantation models: the orthotopic transplantation method, which mimics all steps of metastasis, or intra-circulation injection method. We then performed data-mining and network analysis of gene expression profiles of metastatic cell lines established by each transplantation method. Transcriptome analysis of seven metastatic cell lines revealed novel lung metastasis signature genes, including known metastasis promoting genes and signature genes. In the OXconc (orthotopic xenograft concentration) signature, 'chemotaxis' and 'cell adhesion' terms were enriched. In the TVIconc (tail vein injection concentration) signature, 'antigen recognition' and 'cell adhesion' were enriched. Furthermore, network analysis of the metastasis signature genes highlighted hub genes in the gene regulatory network. Our findings show that expression profiles of highly metastatic cell lines were different between the orthotopic transplantation and intra-circulation injection method. It also indicates that some metastatic signature genes have been missed in previous studies. Characterization of metastasis genes using the orthotopic transplantation method will be helpful in understanding the multi-step mechanisms of metastasis. Signature genes in OXconc may have the potential to become prognostic markers.

    Original languageEnglish
    Pages (from-to)497-504
    Number of pages8
    JournalInternational Journal of Oncology
    Volume50
    Issue number2
    DOIs
    Publication statusPublished - 2017 Feb 1

    Fingerprint

    Gene Regulatory Networks
    Transplantation
    Breast Neoplasms
    Neoplasm Metastasis
    Injections
    Genes
    Cell Line
    Heterografts
    Cell Adhesion
    Lung
    Data Mining
    Gene Expression Profiling
    Chemotaxis
    Cardiovascular System
    Transcriptome
    Veins
    Animal Models
    Antigens

    Keywords

    • Breast cancer
    • DNA microarray
    • Gene regulatory network
    • Metastasis
    • Orthotopic xenograft
    • Transcriptome

    ASJC Scopus subject areas

    • Oncology
    • Cancer Research

    Cite this

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    title = "Comparative analysis of gene regulatory networks of highly metastatic breast cancer cells established by orthotopic transplantation and intra-circulation injection",
    abstract = "Metastasis signature genes in breast cancer have been studied comparing transcriptomic profiles of highly metastatic cancer cell lines established by intra-circulation injection with that of their parental cell line. However, this method is not suitable to analyze the initial steps of metastasis including invasion into local tissues and the circulatory system. To characterize the molecular mechanisms of early metastasis, we established highly metastatic MDA-MB-231 cell lines that metastasized to lung by the two animal transplantation models: the orthotopic transplantation method, which mimics all steps of metastasis, or intra-circulation injection method. We then performed data-mining and network analysis of gene expression profiles of metastatic cell lines established by each transplantation method. Transcriptome analysis of seven metastatic cell lines revealed novel lung metastasis signature genes, including known metastasis promoting genes and signature genes. In the OXconc (orthotopic xenograft concentration) signature, 'chemotaxis' and 'cell adhesion' terms were enriched. In the TVIconc (tail vein injection concentration) signature, 'antigen recognition' and 'cell adhesion' were enriched. Furthermore, network analysis of the metastasis signature genes highlighted hub genes in the gene regulatory network. Our findings show that expression profiles of highly metastatic cell lines were different between the orthotopic transplantation and intra-circulation injection method. It also indicates that some metastatic signature genes have been missed in previous studies. Characterization of metastasis genes using the orthotopic transplantation method will be helpful in understanding the multi-step mechanisms of metastasis. Signature genes in OXconc may have the potential to become prognostic markers.",
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    T1 - Comparative analysis of gene regulatory networks of highly metastatic breast cancer cells established by orthotopic transplantation and intra-circulation injection

    AU - Nakayama, Jun

    AU - Ito, Emi

    AU - Fujimoto, Jiro

    AU - Watanabe, Shinya

    AU - Senba, Kentaro

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