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Extracellular Vesicles: Promises and Pitfalls

April 12–13, 2014

Chaired By

 Clark C. Chen, MD, PhD of University of California San Diego

Meeting Description

Exosomes are small secreted vesicles that contain select proteins, mRNAs, and miRNAs. The available data suggest that exosomes serve as a mean by which glioblastoma can communicate with and modify its neighboring cells and the microenvironment. I am interested in the clinical application of exosomes in terms in neuro-oncology as it pertains to both biomarker and therapeutic development. It is known that glioblastoma cells secrete exosomes containing select tumor protein, mRNA, and miRNAs. The lipid bi-layer of the exosome protects these molecules from degradation in the hostile environment of the various bio-fluids (e.g. urine, serum, cerebrospinal fluid). As such, development of methods for purifying glioblastoma specific exosomes constitutes an attractive strategy for biomarker development. This is particularly important for brain cancers where repeated biopsy is associated with significant surgical and thus not practical in clinical practice. Additionally, fusion of exosomes with peri-tumor stroma or with neighboring tumor cells results in the delivery of exosome contents into these cells. This delivery can significantly alter the biology of the target cell and induce changes in tumor behavior and response to therapy.

While there is general agreement that exosomes are small secreted vesicles that contain select proteins, mRNAs, and miRNAs, there is little agreement in terms of the specific definition of exosomes. The confusion in literature is largely related to a lack of understanding basic exosome biology. In general, exosomes are purified by size based criteria whereby cells and large cellular debris are removed by either centrifugation or size exclusion. In this context, it is not surprising that there are disagreements as to the definition of exosomes. Some authors define exosomes as vesicles of 30-90 nm and vesicles larger vesicles as ectosomes. Others define the upper limits of exosomes as 120-140 nm. While a size-based definition of exosomes will, by nature, be somewhat arbitrary, a more important issue in the field is that there are significant molecular heterogeneity within exosomes purified based on size criteria. It would be greatly advance the field if we come to a consensus of exosome markers that define the exosomes based on the mechanism of formation , the source of origin (urine, serum, cerebrospinal fluid), and aberrant cell states (tumor versus normal). It is further helpful to identify the molecular pathways required for exosome formation. Inhibition of these pathways may hamper communications within the tumor microenvironment and prohibit glioblastoma growth. I hope to address these issues by assembling a panel of exosome investigators.

Meeting Summary
Forum summary not available at this time.
Forum Participants

Andrew Baird, PhD
University of California San Diego, Department of Surgery

Vishal Bansal, MD
University of California San Diego, Department of Surgery

Xandra Breakefield, PhD
Massachusetts General Hospital

Bob Carter, MD, PhD
UC San Diego School of Medicine

Clark Chen, MD, PhD
University of California San Diego

Emanuele Cocucci, MD, PhD
Harvard Medical School

Sara Courtneidge, PhD
Sanford-Burnham Medical Research Institute

Crislyn D'Souza-Schorey, PhD
University of Notre Dame

Carsten Fruhbeis
Johannes Gutenberg-Universität Mainz

Neil Gibson, PhD
Regulus Therapeutics

Stephen Gould, PhD
John Hopkins University School of Medicine

Harry Gruber, MD
Tocagen Management Team

James Hagood, PhD
University of California San Diego

Fred Hochberg, MD
Massacusetts General Hospital

Andrew Kummel, PhD
University of California San Diego

Hakho Lee, PhD
Center for Systems Biology, Massachusetts General Hospital, Harvard Medical School

Hon Leong, PhD
London Health Sciences Centre

Donald Lo, PhD
Duke University

Natalie Luhtala
Salk Institute

David Lyden, MD, PhD
Weill Cornell Medical College

Karen Messer, PhD
University of California San Diego

Bradley Messmer, PhD
University of California San Diego

Johan Skog, PhD
Exosome Diagnositc

Evan Snyder, MD PhD
The Burnham Institute

Jean Wang, PhD
University of California San Diego

Alissa Weaver, MD, PhD
Vanderbilt University Medical Center

Maruzio Zanetti, MD
University of California San Diego