Publications

Publications

Enhanced Detection of Cancer Biomarkers in Blood-Borne Extracellular Vesicles Using Nanodroplets and Focused Ultrasound

Cancer Res. 2017 Jan 1;77(1):3-1

Paproski RJ, Jovel J, Wong GK, Lewis JD, Zemp RJ.

Abstract

The feasibility of personalized medicine approaches will be greatly improved by the development of noninvasive methods to interrogate tumor biology. Extracellular vesicles shed by solid tumors into the bloodstream have been under recent investigation as a source of tumor-derived biomarkers such as proteins and nucleic acids. We report here an approach using submicrometer perfluorobutane nanodroplets and focused ultrasound to enhance the release of extracellular vesicles from specific locations in tumors into the blood. The released extracellular vesicles were enumerated and characterized using micro flow cytometry. Only in the presence of nanodroplets could ultrasound release appreciable levels of tumor-derived vesicles into the blood. Sonication of HT1080-GFP tumors did not increase the number of circulating tumor cells or the metastatic burden in the tumor-bearing embryos. A variety of biological molecules were successfully detected in tumor-derived extracellular vesicles, including cancer-associated proteins, mRNAs, and miRNAs. Sonication of xenograft HT1080 fibrosarcoma tumors released extracellular vesicles that contained detectable RAC1 mRNA with the highly tumorigenic N92I mutation known to exist in HT1080 cells. Deep sequencing serum samples of embryos with sonicated tumors allowed the identification of an additional 13 known heterozygous mutations in HT1080 cells. Applying ultrasound to HT1080 tumors increased tumor-derived DNA in the serum by two orders of magnitude. This work is the first demonstration of enhanced extracellular vesicle release by ultrasound stimulation and suggests that nanodroplets/ultrasound offers promise for genetic profiling of tumor phenotype and aggressiveness by stimulating the release of extracellular vesicles.

PubMed

Download PDF

Stay Informed

To stay up to date on all the latest news and publications, subscribe to our newsletter!

Our First Participant!

Thanks to the participation from men with suspected prostate cancer and men diagnosed with prostate cancer, we will be able to measure if our “tests” can reveal the true nature of prostate cancer and if the tests or biomarkers can diagnose prostate cancer and tell us what cancers are more aggressive.

As part of the Alberta Prostate Registry and Biorepository, patients will be entered into our study, in which blood and other samples are collected over time and their health outcomes are recorded over many years. Patients will follow standard medical advice and care through their doctors. Our team collect biospecimens and information related to general health and cancer behavior over time.

Rather than being frightened by the word ‘cancer’, we want to learn how to predict serious and morbid prostate cancer complications well before they happen, so that we can weigh carefully the pros and cons of available treatments.

In the process, we expect to identify new and important advantage points for better therapies to be developed. The word “cancer” may be scary, but what is truly scary is unawareness.

“It makes me very happy to be able to contribute to find better ways to diagnose prostate cancer.”

- Mr. Garcia

Our International Network of Partners

Meeting these ambitious goals will not be possible without the committed engagement of our many partners across Alberta, Canada and the World. Learn more about our Partners.