Poster Presentation 2019 Hunter Cell Biology Meeting

Predicting cancer spread before it happens – implications for anti-invasive intervention (#104)

Daniel Reed 1 , Sean C Warren 1 , Max Nobis 1 , Pauline Melenec 1 , David Gallego-Ortega 1 , Aurelie S Cazet 1 , Douglas Strahdee 2 , Jody Haigh 3 , Owen J Sansom 2 , Jennifer P Morton 2 , Kurt I Anderson 2 , David Herrmann 1 , Paul Timpson 1
  1. Garvan Institute / The Kinghorn Cancer Centre, Darlinghurst, NSW, Australia
  2. Cancer Research UK Beatson Institute, Glasgow, UK
  3. Monash University, Clayton

 

E-cadherin-mediated cell-cell junctions play a prominent role in maintaining epithelial architecture. Their dysregulation in cancer can lead to the collapse of tumour epithelia and subsequent invasion and metastasis. Recent evidence suggests that, apart from modulating E-cadherin expression, cells are able to mobilise E-cadherin within their cell-cell junctions upon migration and invasion. We have developed new tools to assess the spatiotemporal dynamics of epithelial tumour cell-cell junctions to study the earliest stages of invasion and metastasis.

 

Methods:

Here, we have generated an E-cadherin-GFP mouse, which enables intravital quantification of E-cadherin clustering and mobility to provide insight into tumour cell-cell junction strength and integrity in intact tissues and tumours.

 

Results: We reveal that:

(1) E-cadherin mobility and clustering become de-regulated in invasive and metastatic tumours compared to healthy tissues and non-invasive pancreatic tumours.

(2) These subcellular aberrations in E-cadherin dynamics can be targeted with anti-invasive treatment to re-stabilise cell-cell junctions and to reduce cancer invasiveness.

 

Discussion: We suggest that these techniques can be used as:

(1) novel tools to fundamentally expand our understanding of cell-cell junction dynamics in vivo in native microenvironments

(2) novel pre-clinical drug-screening platform to predict cancer spread and to estimate the efficacy of anti-invasive treatment.