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

  • Authors:
    • Jun Nakayama
    • Emi Ito
    • Jiro Fujimoto
    • Shinya Watanabe
    • Kentaro Semba
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  • Published online on: December 16, 2016     https://doi.org/10.3892/ijo.2016.3809
  • Pages: 497-504
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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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February-2017
Volume 50 Issue 2

Print ISSN: 1019-6439
Online ISSN:1791-2423

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Spandidos Publications style
Nakayama J, Ito E, Fujimoto J, Watanabe S and Semba K: Comparative analysis of gene regulatory networks of highly metastatic breast cancer cells established by orthotopic transplantation and intra-circulation injection. Int J Oncol 50: 497-504, 2017
APA
Nakayama, J., Ito, E., Fujimoto, J., Watanabe, S., & Semba, K. (2017). Comparative analysis of gene regulatory networks of highly metastatic breast cancer cells established by orthotopic transplantation and intra-circulation injection. International Journal of Oncology, 50, 497-504. https://doi.org/10.3892/ijo.2016.3809
MLA
Nakayama, J., Ito, E., Fujimoto, J., Watanabe, S., Semba, K."Comparative analysis of gene regulatory networks of highly metastatic breast cancer cells established by orthotopic transplantation and intra-circulation injection". International Journal of Oncology 50.2 (2017): 497-504.
Chicago
Nakayama, J., Ito, E., Fujimoto, J., Watanabe, S., Semba, K."Comparative analysis of gene regulatory networks of highly metastatic breast cancer cells established by orthotopic transplantation and intra-circulation injection". International Journal of Oncology 50, no. 2 (2017): 497-504. https://doi.org/10.3892/ijo.2016.3809