Improving diagnosis of metastasis
Metastasis is the process by which cancer cells leave the original tumour site and through circulation migrate to the rest of the body. Circulating (CTC) and disseminated tumour cells (DTC) land in different organs and form new cancer sites. Dissemination of tumour cells or metastasis constitutes a major problem in solid tumour progression. The EU-funded initiative 'Molecular signatures as diagnostic and therapeutic targets for disseminated epithelial malignancies' (Dismal) combined the expertise of academic and commercial partners to improve the sensitivity and specificity of diagnostic methods for DTC, primarily focusing on epithelial cancer. Project members generated a cancer tissue biobank encompassing patient primary epithelial tumour tissue and material from common micrometastatic sites. All samples were complemented by patient data and experimental results, including proteomic and genomic array data. Extensive bioinformatic analysis identified common signalling pathways and genes that are involved in the tumour dissemination process. These 'molecular signatures' were linked to DTC detection and progression. To functionally analyse and model DTC, a mouse mammary carcinoma stem cell line was developed (GeTo cells). These cells served as a culture model to investigate potential target genes in vitro. Additionally, GeTo cells were used in an animal model of breast carcinogenesis to identify genes or proteins associated with the metastatic cascade. Overall, study results provided new knowledge on the biology of tumour metastasis, aiding the generation of an improved detection platform that will increase diagnostic precision of disseminated epithelial malignancies.
