Poster Presentation 14th International Biennial Conference on Metastasis Research 2012

Molecular analysis of circulating (CTC) and disseminated tumour cells (DTC) in human breast cancer xenograft models. (#93)

Anthony Tachtsidis 1 2 , Tony Blick 1 , Devika Gunasinghe 2 , Peter F.M Choong 2 3 , Mark Waltham 1 , Alex Dobrovic 4 , Erik W Thompson 1 2
  1. St. Vincent's Institute, Fitzroy, VIC, Australia
  2. Surgery, University of Melbourne, Melbourne, VIC, Australia
  3. Orthopaedics, St Vincent's Hospital, Melbourne, VIC, Australia
  4. Peter MacCallum Cancer Centre, Melbourne, VIC, Australia

Our goal is to establish reproducible and robust mouse models for use in breast cancer DTC/CTC research. Blood samples, bone marrow and tumour tissue were collected from mice xenografted with the MDA-MB-468 cell line and also using metastatic breast cancer material that was successfully grafted and passaged in vivo (ED-03). Using a species-specific tandem nested qRT-PCR approach, we are able to detect and measure a panel of human specific markers relating to: detection of CTC/DTC, prognostic markers of breast cancer, the ‘cancer stem cell’ phenotype and epithelial-mesenchymal plasticity (EMP). EMP is hypothesised to be involved in the generation and function of DTC/CTC. All samples from each xenograft were assessed and comparisons made between blood, bone marrow and tumour. Analysis of relative expression levels in CTC and DTC compared to tumour of the MDA-MB-468 model revealed statistically significant changes in CD24, CD44, OAZ1, SNAI1, CLDN3 and CLDN4. In the ED03 model, significant changes in relative levels of CDH1, OAZ1, SNAI1, and CK20 were determined. Several other markers between the two models trended towards significance but did not reach a p-value <0.05. Immunohistochemical analysis on cytospin slides of bone marrow from the MDA-MB-468 and ED-03 xenografts has also been conducted and visual confirmation of DTC presence was achieved. These are the first such analyses of human xenograft CTC and DTC.