Cancer-derived exosomes – a source of novel biomarkers and therapeutic targets for gastrointestinal cancers
Title of the project: Cancer-derived exosomes – a source of novel biomarkers and therapeutic targets for gastrointestinal cancers
Funding: Latvian Council of Science
Project number: 625/2014
Project coordinator: Dr.biol. Aija Linē
Collaboration partners: Latvian Biomedical Research and Study Centre, Faculty of Medicine, University of Latvia, Riga East University Hospital, Institute of Microbiology and Biotechnology, University of Latvia
Gastric and colorectal cancers are a major health problem affecting over two million people annually and represent an important clinical challenge with unmet medical needs worldwide. The identification of reliable non-invasive biomarkers for the early detection and monitoring of the disease and the development of novel therapeutic strategies are of paramount importance for reducing the disease burden and mortality. Exosomes – small, cup-shaped extracellular vesicles carrying a variety of lipids, proteins, mRNAs and non-coding RNAs have emerged as important mediators of inter-cellular communication implicated in the regulation of normal biological processes and the development of a variety of diseases, including cancer, and may serve as a novel source of biomarkers and targets for therapeutic intervention. Despite the increasing interest in the exosome biology, a number of fundamental questions regarding the sorting of RNA and protein cargo, the factors determining the recipient cell selection, the mechanisms of uptake and their fate in the recipient cells and the biological effects exosomes cause in the recipient cells are still unclear. Furthermore, to the best of our knowledge, markers that would allow to discriminate between cancer-derived exosomes and normal tissue-derived exosomes have not been identified so far.
The proposed project aims to characterise the RNA and protein content of cancer-derived exosomes in order to identify novel biomarkers for gastrointestinal cancers, to identify hypoxia-regulated exosomal components that may play an important role in the cancer progression and to get a deeper insight into the recipient cell specificity, mechanisms of uptake and the functional role of cancer-derived exosomes in the tumour-host interactions that may serve as a foundation for the development of novel therapeutic approaches.
We propose to tackle these questions by combining cutting edge technologies, such as next generation sequencing, Fourier transform infrared spectroscopy, one- and two-dimensional liquid chromatography-tandem mass spectrometry, live-cell imaging and variety of immunological and cell biology assays. This is a multidisciplinary research programme that requires access to large, well characterized cohorts of GC and CRC patients and controls and expertise in the cancer biology and immunology, pathology, proteomics, cellular and molecular biology, spectroscopy and biochemistry. The project brings together partners from four large research institutions – BMC, LU MF, REUH and LU MBI with high-level expertise in diverse fields that covers all aspects required to achieve the goals of this project.