New cross-disciplinary research led by Queensland scientists from Griffith University, QIMR Berghofer Medical Research Institute and The University of Queensland has made a breakthrough discovery that could inhibit a cholesterol-mediated mechanism that induces metastatic prostate cancers.
The research found that an RNA-binding protein (hnRNPK) released in small particles (exosomes) from prostate cancer cells could transfer oncogenic microRNAs to recipient cells in other parts of the body to induce metastatic cancers.
Dr Alex Cristino, from Griffith Institute for Drug Discovery, said the study revealed the molecular mechanism by which hnRNPK could transfer selected microRNAs to exosomes.
“We are now starting to understand how specific RNA-binding proteins like hnRNPK can guide the export of selected genetic information (in the form of RNA molecules) into nanoparticles to coerce other cells to change their cellular program, for example, to activate metastasis-promoting pathways,” Dr Cristino said.
Harley Robinson, a PhD candidate from The University of Queensland based at QIMR Berghofer, said the hnRNPK protein usually resided in the nucleus of a cell but laboratory tests on prostate cancer cells found the protein outside the nucleus, in the messaging centre where the exosomes were being prepared, and in exosomes that have been released by cells.
“The exosomes act like a pre-planting conditioner that makes the environment in the new parts of the body receptive to the cancer cells when they eventually reach the site,” Ms Robinson said.
“Our lab work showed that reducing the cholesterol levels or boosting OMEGA-3 levels in the cells could stop the hnRNPK message from leaving the cancer cell and spreading its dangerous message.”
Dr Cristino said these extracellular microvesicles played a critical role in cancers and several other biological processes including neuronal development and function, immune response and viral infections.
“This integrated cellular transport system depends on a fine regulation between lipid, protein and RNA interactions that is used by all cells in our body for inter-cellular communication,” Dr Cristino said.
“These findings have promising prospects for novel bio-inspired gene therapy strategies based on designer nanoparticles carrying functional RNA molecules to be delivered to specific cells.”
Senior researcher and head of QIMR Berghofer Medical Research Institute’s Precision and Systems Biomedicine Group, Associate Professor Michelle Hill said cholesterol and OMEGA-3 levels in cells regulated each other but in cancer the balance shifted with cholesterol dominating the cells.
“This understanding of the role cholesterol plays in sending out these metastatic messages to other parts of the body means we could potentially use statins or other cholesterol lowering drugs to prevent metastases,” Associate Professor Hill said.
“Conversely it might be possible to boost OMEGA-3 levels through supplements to protect against cancer spread.
“The findings are very exciting and we think this hnRNPK protein might play a role in metastases in other cancers as well, but it is early days and more research is needed to confirm the link.”
The study was published in Clinical and Translational Medicine.