Poster Presentation 35th Lorne Cancer Conference 2023

Use of optical barcoding to uncover the mechanisms associated with clonal fate in metastatic breast cancer (#150)

Sreeja Gadipally 1 , Jean Berthelet 1 , Delphine Merino 1 , Farrah El-Saafin 1 , Belinda Yeo 1
  1. Olivia Newton-John Cancer Research Institute, Heidelberg, VIC, Australia

Breast cancer is a heterogeneous disease, based on results from emerging single-cell technologies. Tumour cell dynamics and interactions play a significant role in disease spread and treatment resistance. Breast tumours consist of several sub-populations of cells, so-called “clones”, with specific cellular and molecular characteristics. Some cancer clones can be more ‘aggressive’ than others, leading to faster disease progression and drug resistance. Here, we are taking advantage of the Lentiviral Gene Ontology (LeGO) based optical barcoding technology previously used in our laboratory (Berthelet, Wimmer et al., SA 2021) to track the fate of cancer cells in patient derived xenografts and to understand the cellular and molecular bases of human metastases. Cellular barcoding enables the identification of clones that harbour different levels of fitness in distant organs and their characterisation at the molecular level.

To establish barcoded metastatic PDX models, cancer cells were labelled using the LeGO technology and then introduced into the mammary fat pads of immune-deficient mice. At the experimental endpoint, cancer clones were collected from multiple sites and identified by imaging and flow cytometry based on the expression of specific fluorescent tags. Interestingly, comparing the fate of human breast cancer clones injected into multiple mice, we found that some of them may have a higher likelihood to metastasis to specific organs compared to others. Comparing the transcriptomic landscape of these clones after RNA sequencing will enable us to identify the pathways associated with metastasis, aggressiveness, and cellular fitness in vital organs, and target these pathways with clinically relevant therapies.