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Lai et al. J Cancer Metastasis Treat 2019;5:65 Journal of Cancer
DOI: 10.20517/2394-4722.2019.011 Metastasis and Treatment

Review Open Access

Membrane lipid binding molecules for the isolation
of bona fide extracellular vesicle types and

associated biomarkers in liquid biopsy

Ruenn Chai Lai , Kok Hian Tan , Sai Kiang Lim 1,3
2
1
1 A*STAR Institute of Medical Biology, 8A Biomedical Grove, #05-05 Immunos, Singapore 138648, Singapore.
2 Department of Maternal Fetal Medicine, KK Women’s & Children’s Hospital, Singapore 229899, Singapore.
3 Department of Surgery, YLL School of Medicine, NUS, Singapore 119074, Singapore.

Correspondence to: Prof. Sai Kiang Lim, A*STAR Institute of Medical Biology, 8A Biomedical Grove, #05-05 Immunos, Singapore
138648, Singapore. E-mail: saikiang.lim@imb.a-star.edu.sg

How to cite this article: Lai RC, Tan KH, Lim SK. Membrane lipid binding molecules for the isolation of bona fide extracellular
vesicle types and associated biomarkers in liquid biopsy. J Cancer Metastasis Treat 2019;5:65.
http://dx.doi.org/10.20517/2394-4722.2019.011

Received: 17 May 2019 First Decision: 30 Jul 2019 Revised: 7 Aug 2019 Accepted: 29 Aug 2019 Published: 3 Sep 2019

Science Editor: Bingliang Fang Copy Editor: Jia-Jia Meng Production Editor: Tian Zhang

Abstract
Cancer exacts a heavy socioeconomic cost. Earlier detection and treatment are likely to mitigate this cost.
Unfortunately, conventional tissue biopsy, the gold standard in cancer diagnosis cannot fulfill the goal of earlier
detection. While liquid biopsy is a promising alternative to tissue biopsy, it has its challenges and limitations.
A major challenge is the isolation of bona fide lipid membrane vesicles from biological fluids. In this review,
we presented a new perspective of isolating different types of extracellular vesicles (EVs) by their affinity for
membrane lipid binding ligands for liquid biopsy. EVs are lipid membrane particles naturally released by almost all
cells and are found in almost all biological fluids suitable for liquid biopsy. They carry materials from the secreting
cells that could affect the biology of the recipient cells and could thus inform on the state and progress of the
disease. However, isolating bona fide EVs is a technical challenge as biological fluids have a complex composition
and contain particles or aggregates that are physically similar to EVs. Here we review the use of membrane lipid-
binding ligands to isolate different bona fide EV subtypes, and to circumvent the problem of co-isolating physically
similar non-EV complexes in current EV isolation protocols. We will discuss the advantages of this technique
and its potential for accelerated biomarker discovery and validation through examples of pre-clinical studies. We
propose that isolating EV subtypes is a technically viable and robust strategy to overcome the current bottleneck
of isolating EVs for liquid biopsy.

© The Author(s) 2019. Open Access This article is licensed under a Creative Commons Attribution 4.0
International License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use,
sharing, adaptation, distribution and reproduction in any medium or format, for any purpose, even commercially, as long
as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license,
and indicate if changes were made.

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