Recently exosomes, which are small membrane bound vesicles, have been suggested to be one of the key communication processes used by cancer cells to; 1. deliver molecules to other cancer cells to enable them to become metastatic; 2. deliver molecules to the cells supporting the tumour mass to prime them for the cancer cells to leave the tumour mass and 3. deliver molecules to distant organs to prime them to receive the invading cancer cells and allow the formation of a metastasis. However, it remains unknown how exosomes perform these functions and what makes cancer cell exosomes different from the exosomes involved in normal cell cell communications.
The CD9 protein is one of the most ubiquitously expressed proteins on the surface of exosomes and therefore considered an exosome marker. Importantly, CD9 is also known to assist with the suppression of solid tumour metastasis. Despite this, to date there has been no investigation of the specific function of CD9 in exosomes and indeed how exosomes behave if they lose CD9, which is likely to occur as cancers decrease their CD9 production during tumour progression. This study will address these important questions using breast and prostate normal and cancerous cell lines that have specifically had their CD9 expression modified.
Properties of the modified exosomes in regards metastasis will be investigated including their ability to alter the adhesive, invasive and migratory properties of cancer cells to different substrates and other cell types. Changes to exosome content will be assessed to determine what is driving the altered functions observed. This study will significantly advance our understanding of tumour exosomes enabling the development of novel therapeutics to target tumour exosomes for the treatment of metastatic cancer and potentially identify ways to better use tumour exosomes as prognostic biomarkers.
Dr Judith Weidenhofer, Dr Kathryn Skelding, Dr Matt Dun, Ms Belinda Goldie, Ms Danielle Bond