Invasion and Metastasis

Cancer invasion and metastasis occur in a complex three dimensional environment, with reciprocal feedback from the surrounding host tissue and stroma governing cancer cell behaviour. Understanding this behaviour in an intact host setting allows us to examine, in a more physiological context, the aberrant regulation of critical events that lead to dissemination and spread of the primary tumour.  Intravital (in vivo) imaging is providing new insights on how cells behave in their native microenvironment thereby improving our understanding of disease progression.

In our laboratory we use novel state-of-the-art intravital imaging approaches and new fluorescent mouse models to uncouple the metastatic process into key stages in order to pinpoint critical events that drive tumour invasion and metastasis. Our approach permits real-time imaging ranging from whole body tumour progression to single-cell invasion events, and helps us to understand how tumour cell (a) dissociation (b) invasion or (c) progression are controlled and how this is linked to the development of invasive or metastatic cancer.

We also explore properties of the three-dimensional tumour microenvironment that contribute to poor drug targeting in order to pinpoint critical barriers that impair efficient tumour targeting. Combination therapy aimed at counteracting these barriers are then employed to enhance drug penetrance and efficiency in vivo and improve overall drug delivery outcome.

A key to our laboratory’s approach is to use established in vitro and in vivo 2D and 3D technology to examine cancer progression at a sub-cellular and molecular level in situ. Key techniques and current applications include:

  • Fluorescence Lifetime Imaging (FLIM) & Fluorescence Resonance Energy transfer (FRET) analysis allow for accurate, time-dependent, monitoring of signalling events during drug treatment in a live tumour setting.
  • We use Fluorescence Recovery After Photobleaching (FRAP) & Photoactivation in live tumours to examine and predict cell-cell junction turnover during early stages of cancer dissemination and invasion.

3D organotypic matrices serve as a malleable platform for the assessment of vital tumour/stromal interaction in a 3D context, providing a powerful tool to complement in vivo investigations.

Software Tools
Open source tools developed by the Timspon lab are available to download at http://github.com/timpsonlab.

3D Organotypic Matrix Database/Resource
Our 3D Organotypic Matrix Database/Resource contains over 4,000 organotypic invasion samples and embedded tissues.

 

Invasion and Metastasis Group work: Images • Videos

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