From Cardiff Univ.
Exosomes in Cancer Immunology
Introduction
Exosomes are small vesicles (of around 40-90nm diameter), originating from within multivesicular bodies, which are subsequently secreted into the extracellular space. Exosomes are produced my most/all cell types, and have a molecular phenotype which largely reflects that of the parent cell. The exosome membrane is lipid-raft like, comprising a host of transmembrane and GPI-linked molecules. The lumen is also complex, and may act as a means of delivering molecules from cell to cell.
Exosomes express a complex array of membrane and intralumenal proteins. There may also be mRNA encapsulated within the vesicle, which may be functionally important as can be seen in the above picture.
Research Interests
Exosomes and Cancer Immunology:
Exosomes produced by cancer cells are compositionally different from those produced by non-cancer cells, in that they express tumour-associated antigens. Exosomes may be an efficient mode for delivering these antigens to dendritic cells, and as such may be useful as cancer vaccines. Because cancer-exosomes are very complex, we have also been investigating the possible inhibition of correct immune function(s) driven by exosomes, and our research is helping to define exosomes as a major mechanism of cancer immune evasion. We are currently focussing on exosomes isolated from prostate cancer, and pleural malignant mesothelioma. The following picture shows Prostate Cancer Cells (LNCap) in culture.
Exosomes in cell to cell communication:
The surface of exosomes is covered in molecules that may function in delivering signals to target cells. Integrins, for example, expressed by exosomes from diverse cell types may serve such a function. Under conditions that mimic inflammation, some cells (including fibroblasts), express elevated levels of integrin ligands (e.g. ICAM-1). Exosomes are capable of stimulating Calcium Signalling in such cells, through integrin dependent adhesion. Collaborators in such studies include Dr Maurice Hallett, Neutrophil Signalling Group, Dept of Surgery, and Dr Robert Steadman, Institute of Nephrology. Exosome coated beads (yellow) triger transient Calcium flux (increasing green) in fibroblasts following exosome-fibroblast contact are shown in the following picture.
Exosomes as Cancer Biomarkers:
Recent investigations by us and others have shown exosomes can be isolated from body-fluids including urine. It may be that analysis of the protein repertoire of such readily obtained exosomes will provide information that is clinically useful, about disease status (diagnosis, and monitoring). Current studies to evaluate exosomes in bladder cancer are underway, with collaborators; Dr John Staffurth, Oncology and Dr Ian Brewis, under the auspices of the Cardiff Proteomics Centre . Silver stained gel showing purification of urinary exosomes can be seen below.
AI
