Extracellular Vesicles: Promises and Pitfalls

Clark C.
Chen
,
MD, PhD
University of Minnesota

Forum 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.

Forum Summary

Venue & Travel Information

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  • Travel Confirmation will be sent out within 1 week of the meeting. This will include a hotel confirmation number, if there is one, and airport transfer details. We have to wait until we receive almost everyone’s travel to book airport transfer. Due to frequent airline changes, we wait until the week of the meeting to send this out.
  • Airport transfer is provided by Foundation staff, volunteers or arranged shuttle at specific times. If you opt to utilize Foundation airport transportation on your travel form, please be patient in receiving this information. We will send it to the week of the meeting.
  • Speaker agenda is not sent out prior to the meeting. It will be provided upon arrival in the meeting packet. We do not tell people when they are speaking because we expect everyone to attend all sessions. Sessions are all day Friday and Saturday.
  • Frequently airport transfer is provided by volunteers. Please be patient on receiving this information. Airport transfer will be sent out prior to arrival.
  • REMINDER: We do not reimburse for home side airport transfer or incidentals while traveling. We will not honor miscellaneous receipts sent for these expenses.

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
Emanuele
Cocucci
,
MD, PhD
Harvard Medical School
Sara A.
Courtneidge
,
PhD
Oregon Health & Science University
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

Forum Scholars

No Scholars attended this meeting