Blood-Based Gene Expression Signatures in Non-Small Cell Lung Cancer.Clin Cancer Res. 2011 May 15 Thomas Zander, Andrea Hofmann, Andrea Staratschek-Jox, et al has been big in the international news recently. The authors are aiming to develop an RNA-stabilized blood test for asymptomatic lung cancer, using gene expression profiles, from what they believe to be immune effector blood cells – not cancer cells. The prognosis for lung cancer once you already have symptoms, is terrible. Their work is great news because this kind of non-invasive diagnostic test is desperately needed.
However, there is another promising approach to transcriptome signature diagnostics to be aware of…Microvesicle shuttled RNA.
Microvesicles, (MV), were once considered just cellular debris. We now know that blood, and many other body fluids, carry MVs which have important roles in cell to cell signaling. Microvesicles are released by cells’ plasma membrane, at sizes up to 1500nm, or they are released from the endosomal membranes, at sizes from 30-100nm, in which case, they are called exosomes. They carry bioactive lipids, proteins, DNA, mRNA, miRNA, and transposons, …and sometimes virus, prions or mitochondria…all specific to their originating cell. The majority of MVs come from Platelet, Endothelial- and Leukocyte cells. Their primary known effects are blood clotting, chemotaxis and immune response. However, subpopulations of MVs can have disease enhancing effects – as in the cases of virally infected, or cancerous originator cells. Cancer cells produce higher levels of microvesicles in the blood. Many important cell to cell signaling roles have already been established for MVs. It all depends on their cargo.
The exosome’s shielded MicroRNA (miRNA) cargo is an especially promising candidate for cancer profiling. For example, miRNAs called “Oncomirs” regulate the mRNAs for oncogenic proteins. “Angiomirs” likewise, are miRNAs which regulate mRNAs for angiogenic proteins. MicroRNAs have been implicated in cancer stem cell drug resistance. It is likely that exosomes shuttling RNA from cancer cell originators promote metastatic cancer through epigenetic effects. MicroRNA are also more stable than protein exosomal cargo, in freezing, thawing or fixing of body fluid samples. Advances in transcriptome analysis using next generation sequencing can be put to good use here.
Here is a list of several exosome translational research investigations, for epigenetics experts to be aware of. This is an area to watch.
- A pilot study clinical trial of Tumor-Derived Exosomes as Diagnostic and Prognostic Markers in Breast Cancer Patients Receiving Neoadjuvant Chemotherapy – is being sponsored by the Leo W. Jenkins Cancer Center in North Carolina.
- Exosomes for targeted siRNA delivery
- Dendritic cell-derived exosomes (Dex) Phase II Clinical trial in France, testing their cancer immunotherapy potential, (exosome therapy potential I am mentioning, as an aside).
- Hemopurifier® is a new medical selective filtration device which can be used to bind disease-enhancing exosomes, and remove them from circulation. The device is produced by Aethlon Medical. Aethlon Medical owns Exosome Sciences, Inc ,which is developing in vitro diagnostic tests.
- The Arizona based company Caris Life Sciences, develops and provide diagnostic services, with a platform which uses antibodies to capture microvesicle to then profile. Please see their video below.