Multi-modal liquid biopsy platform for cancer screening: screening both cancer-associated rare cells and cancer cell-derived vesicles on the fabric filters for a reliable liquid biopsy analysis

Jiyoon Bu,Tae Hee Lee,Young-Ho Cho,Jae-Eul Shim

doi:10.1186/s40580-019-0204-3

Jiyoon Bu, Tae Hee Lee + Show 2 more

Open Access

https://doi.org/10.1186/s40580-019-0204-3

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Abstract

Circulating tumor cells (CTCs) are receiving a great amount of scientific interest as a diagnostic biomarker for various types of cancer. Despite the recent progress in the development of highly sensitive CTC isolation devices, post-capture analysis of CTCs is still hindered by technical challenges associated with their rarity. Herein, we present a multi-modal CTC screening platform which is capable to analyze CTCs and CTC-derived extracellular vesicles (EVs), simultaneously from a single sample. Cytochalasin B (CB) treatment promotes cells to release large number of EVs from their surface, as demonstrated by CB-treated cells (5 µg/mL for 3 h) secreting 3.5-fold more EVs, compared to the non-treated cells. CB further generates 1.7-fold more EVs from the cells captured on our CTC filtration device (the fabric filter), compared to those from the cell culture flasks, owing to its multiple pore structure design which reduces the non-specific binding of EVs. Both CB-treated cancer cells and CB-induced EVs are found to overexpress tumor-associated markers, demonstrating a potential for the development of CTC dual-screening platform. Collectively, the results presented in this study reveal that our multi-modal cancer screening platform can synergistically improve the reliability and efficacy of the current CTC analysis systems.

Highlights

Image-guided tissue biopsy is utilized as the standard diagnostic test for cancer [1]
These extracellular vesicles (EVs) have been exploited in a wide range of biomedical applications, as they are known to reflect the biological characteristics of the parental cells that they have been originated from [28]
The smaller slot width of prototype 1 (P1) was effective on capturing tumor cells with higher sensitivity compared to prototype 2 (P2), which we have demonstrated from our still sufficiently presented on the surface of Cytochalasin B (CB)-treated MCF-7 cells

Summary

Introduction

Image-guided tissue biopsy is utilized as the standard diagnostic test for cancer [1]. This traditional biopsy technique has facilitated histological and molecular analysis of tumors, improving the clinical outcomes [2]. The results obtained from these biopsy tests often show inconsistent benefits since tumors grow, mutate, and become heterogeneous [2, 3]. Different biomarkers have been employed for the diagnosis and prognosis of tumor. Tumor-associated antigens are one of the most well-established biomarkers that are already in clinical use [5].

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