If You Don’t Look, You Won’t See: Intravital Multiphoton Imaging of Primary and Metastatic Breast Cancer

  • Laura Bonapace
  • Jeffrey Wyckoff
  • Thomas Oertner
  • Jacco Van Rheenen
  • Tobias Junt
  • Mohamed Bentires-AljEmail author


A fundamental hallmark of cancer is progression to metastasis and the growth of breast cancer metastases in lung, bone, liver and/or brain causes fatal complications. Unfortunately, the cellular and biochemical mechanisms of the metastatic process remain ill-defined. Recent application of intravital multiphoton microscopy (MP-IVM) to image fluorescently labeled cells in mouse models of cancer has allowed dynamic observation of this multi-step process at the cellular and subcellular levels. In this article, we discuss the use of MP-IVM in studies of breast cancer metastasis, as well as surgical techniques for exposing tumors prior to imaging. We also describe a versatile multiphoton microscope for imaging tumor-stroma interactions.


Multiphoton microscopy Intravital imaging Breast cancer Metastasis 



Multiphoton intravital microscopy


Multiphoton microscopy


Second harmonic generation


Photomultiplier tube


Fluorescence-lifetime imaging microscopy


Fluorescence resonance energy transfer



We thank J. Rietdorf and S. Bundschuh (FMI) for helping us set up the MPM and R. Friedrich (FMI) and J. Stein (Theodor Kocher Institute, Bern) for helpful discussions. We thank A. de Graaff and the Hubrecht Imaging Center for their support. Research in the lab of JvR is supported by VIDI fellowships (91710330), equipment grants (175.010.2007.00) and (834.11.002) from the Dutch Organization of Scientific Research (NWO), and a grant from the Dutch Cancer Society (KWF: HUBR 2009–4621). Research in the lab of M.B-A. is supported by the Novartis Research Foundation, the European Research Council (ERC starting grant 243211-PTPsBDC), the Swiss Cancer League, and the Krebsliga Beider Basel.


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Copyright information

© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  • Laura Bonapace
    • 1
    • 2
  • Jeffrey Wyckoff
    • 1
  • Thomas Oertner
    • 1
  • Jacco Van Rheenen
    • 3
  • Tobias Junt
    • 2
  • Mohamed Bentires-Alj
    • 1
    Email author
  1. 1.Friedrich Miescher Institute for Biomedical Research (FMI)BaselSwitzerland
  2. 2.Novartis Institutes for Biomedical ResearchBaselSwitzerland
  3. 3.Hubrecht Institute-KNAW and University Medical Center UtrechtUtrechtThe Netherlands

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