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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

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APCaRI is part of the Movember Prostate Cancer Outcomes network

The Prostate Cancer Outcomes Global Initiative to Compare and Reduce Variation is a project led by Movember aiming to improve health outcomes for men throughout their prostate cancer journey by focusing on variation in care and engaging clinicians and researchers across 14 countries worldwide.

The international team will collect data from prostate cancer patients segmented into the categories of data items as outlined by the International Consortium for Health Outcomes Measurement (ICHOM). These include patient factors, baseline tumor factors, pathological information, treatment variables, acute complications of treatment, and survival and disease control).

The Alberta Prostate Cancer dataset is highly aligned with the ICHOM standards. This means that we can effectively compare treatments and outcomes in Alberta with teams around the world to find ways to improve our care at home and abroad!

This is the result of hours of planning and true team work lead by Dr. Trafford Crump, the APCaRI Scientific and Data Quality Committee, and the APCaRI clinical, scientific, research and pathology teams. Thanks to your efforts, we are one step closer to improving patient outcomes.

- John Lewis