Journal
NEW BIOTECHNOLOGY
Volume 49, Issue -, Pages 77-87Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.nbt.2018.09.004
Keywords
Circulating tumour cells; Glycosylation; Microfluidics; Cancer; Liquid biopsy; Lab-on-a-chip
Funding
- Portuguese Foundation for Science and Technology (FCT) [SFRH/BD/105355/2014, SFRH/BD/111242/2015, SFRH/BD/103571/2014, SFRH/BD/127327/2016, SFRH/BPD/101827/2014, SFRH/BPD/111048/2015]
- European Social Fund (ESF) under Human Potential Operation Programme (POPH) from National Strategic Reference Framework (NSRF)
- Portuguese Oncology Institute of Porto Research Centre [CI-IPOP-29-2014, CI-IPOP-58-2015]
- FEDER funds through the Operational Programme for Competitiveness Factors-COMPETE [POCI-01-0145-FEDER-016585, POCI-01-0145-FEDER-007274]
- FCT [PTDC/BBB-EBI/0567/2014, UID/BIM/04293/2013, PEst-OE/SAU/UI0776/201]
- PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund (ERDF) [NORTE-45-2015-02]
- Portuguese Digestive Cancer Investigation Group (GICD)
- [NORTE-01-0145-FEDER-000029]
- Fundação para a Ciência e a Tecnologia [SFRH/BD/127327/2016, SFRH/BPD/101827/2014, SFRH/BD/103571/2014] Funding Source: FCT
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Circulating tumour cells (CTCs) originating from a primary tumour, lymph nodes and distant metastases hold great potential for liquid biopsies by providing a molecular fingerprint for disease dissemination and its temporal evolution through the course of disease management. CTC enumeration, classically defined on the basis of surface expression of Epithelial Cell Adhesion Molecule (EpCAM) and absence of the pan-leukocyte marker CD45, has been shown to correlate with clinical outcome. However, existing approaches introduce bias into the subsets of captured CTCs, which may exclude biologically and clinically relevant subpopulations. Here we explore the overexpression of the membrane protein O-glycan sialyl-Tn (STn) antigen in advanced bladder and colorectal tumours, but not in blood cells, to propose a novel CTC isolation technology. Using a size-based microfluidic device, we show that the majority (> 90%) of CTCs isolated from the blood of patients with metastatic bladder and colorectal cancers express the STn antigen, supporting a link with metastasis. STn(+) CTC counts were significantly higher than EpCAM-based detection in colorectal cancer, providing a more efficient cell-surface biomarker for CTC isolation. Exploring this concept, we constructed a glycan affinity-based microfluidic device for selective isolation of STn(+) CTCs and propose an enzyme-based strategy for the recovery of viable cancer cells for downstream investigations. Finally, clinically relevant cancer biomarkers (transcripts and mutations) in bladder and colorectal tumours, were identified in cells isolated by microfluidics, confirming their malignant origin and highlighting the potential of this technology in the context of precision oncology.
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