Using organoids to understand the role of tumour suppressors in colorectal cancer
Colorectal cancer (CRC) affects both men and women and comes third after lung and breast cancer, as one of the most common cancer types worldwide. In Nordic countries it is the second most common cancer after breast cancer. Importantly, CRC has shown an increase in incidence in Norway over the last 50 years. Most adult cancers are carcinomas that arise from epithelial cells. During cancer progression, epithelial organization is lost as cells lose contacts with their neighbours and become more motile and invasive. This change from an epithelial-to-mesenchymal morphology (EMT) is associated with poor prognosis. It is therefore highly relevant to study processes that regulate epithelial integrity and to identify regulators of this process.
Figure legend. Colorectal Caco-2 cells embedded in matrigel form a polarised epithelium surrounding a single lumen when embedded in matrigel. Cells have been fixed, permeabilised and stained for proteins that label the apical membrane (red) and the basolateral membrane (green). DNA is labelled with Hoechst (blue).
Intestinal stem cells grown in matrigel, an extracellular matrix component that mimics the extracellular environment, can differentiate into epithelial organoids containing all cell types of the colon. These have become attractive models to study colorectal cancer since they closely resembles in vivo patient organ biology, are accessible to functional studies and importantly, response to pharmacological treatments mimics the individual patient’s in vivo response.
This project will aim to elucidate the role of specific tumour suppressors in epithelial morphogenesis using intestinal organoids. Techniques that will be learned include cell culture, immunofluorescence, confocal microscopy, siRNA transfections, generation of stable cell lines and CRISPR-Cas9 gene editing.
Research will be located at the Institute for Cancer Research, Oslo University Hospital at the Radium Hospital, department of Molecular Cell Biology. Our research group is part of the newly appointed centre of excellence CanCell, which started in January 2018. The research environment is excellent and stimulating for young scientists.