Emerging Technologies for Cancer Research: Towards Personalized Medicine with Microfluidic Platforms and 3D Tumor Models

In the present review, we describe three hot topics in cancer research such as circulating tumor cells, exosomes, and 3D environment models. The first section is dedicated to microfluidic platforms for detecting circulating tumor cells, including both affinity-based methods that take advantage of antibodies and aptamers, and “label-free” approaches, exploiting cancer cells physical features and, more recently, abnormal cancer metabolism. In the second section, we briefly describe the biology of exosomes and their role in cancer, as well as conventional techniques for their isolation and innovative microfluidic platforms. In the third section, the importance of tumor microenvironment is highlighted, along with techniques for modeling it in vitro. Finally, we discuss limitations of two-dimensional monolayer methods and describe advantages and disadvantages of different three-dimensional tumor systems for cell-cell interaction analysis and their potential applications in cancer management.

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In vitro culturing of circulating tumor cells in lung cancer management

Lung Cancer ◽

10.1016/j.lungcan.2012.05.039 ◽

2012 ◽

Vol 77 ◽

pp. S23

Author(s):

Katarína Kološtová ◽

Marián Liberko ◽

Eva Hroncová ◽

Robert M. Hoffman ◽

Vladimír Bobek

Keyword(s):

Lung Cancer ◽

Tumor Cells ◽

Circulating Tumor Cells ◽

Cancer Management

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Label-Free Enrichment and Molecular Characterization of Viable Circulating Tumor Cells from Diagnostic Leukapheresis Products

Clinical Chemistry ◽

10.1373/clinchem.2018.296814 ◽

2019 ◽

Vol 65 (4) ◽

pp. 549-558 ◽

Cited By ~ 15

Author(s):

André Franken ◽

Christiane Driemel ◽

Bianca Behrens ◽

Franziska Meier-Stiegen ◽

Volker Endris ◽

...

Keyword(s):

In Vitro Culture ◽

Cancer Patients ◽

Tumor Cells ◽

Circulating Tumor Cells ◽

Peripheral Blood ◽

Label Free ◽

Breast Cancer Patients ◽

Large Numbers ◽

Genomic Aberrations

AbstractINTRODUCTIONCirculating tumor cells (CTCs) may be used to improve cancer diagnosis, prognosis, and treatment. However, because knowledge regarding CTC biology is limited and the numbers of CTCs and CTC-positive cancer patients are low, progress in this field is slow. We addressed this limitation by combining diagnostic leukapheresis (DLA) and microfluidic enrichment to obtain large numbers of viable CTCs from metastasized breast cancer patients.METHODSDLA was applied to 9 patients, and 7.5 mL of peripheral blood was drawn. CTCs were enriched with the Parsortix™ system. The quality of CTCs from fresh and cryopreserved DLA products was tested, and CTCs were cultured in vitro. Single uncultured and cultured CTCs were isolated by micromanipulation to determine different parameters, such as genomic aberrations and mutation profiles of selected tumor-associated genes. Expression levels of estrogen receptor and HER2/neu were monitored during in vitro culture.RESULTSViable CTCs from peripheral blood and fresh or frozen DLA products could be enriched. DLA increased the likelihood of successful CTC culture. Cryopreserved DLA products could be stored with minimal CTC loss and no overt reduction in the tumor cell quality and viability during an observation period of up to 3 years. The analyzed parameters did not change during in vitro culture. DLA samples with high CTC numbers and lower ratios of apoptotic CTCs were more likely to grow in culture.CONCLUSIONSThe increased CTC numbers from fresh or cryopreserved DLA products facilitate multiple functional and molecular analyses and, thus, could improve our knowledge of their biology.

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Molecular in vitro diagnostic examinations - Specifications for pre-examination processes for circulating tumor cells (CTCs) in venous whole blood

10.3403/30409968u ◽

2020 ◽

Keyword(s):

Tumor Cells ◽

Circulating Tumor Cells ◽

Whole Blood ◽

In Vitro Diagnostic

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Molecular in vitro diagnostic examinations - Specifications for pre-examination processes for circulating tumor cells (CTCs) in venous whole blood

10.3403/30409968 ◽

2020 ◽

Keyword(s):

Tumor Cells ◽

Circulating Tumor Cells ◽

Whole Blood ◽

In Vitro Diagnostic

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Molecular in vitro diagnostic examinations - Specifications for pre-examination processes for circulating tumor cells (CTCs) in venous whole blood

10.3403/30409967u ◽

2020 ◽

Keyword(s):

Tumor Cells ◽

Circulating Tumor Cells ◽

Whole Blood ◽

In Vitro Diagnostic

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Molecular in vitro diagnostic examinations - Specifications for pre-examination processes for circulating tumor cells (CTCs) in venous whole blood

10.3403/pdcents17390 ◽

2020 ◽

Keyword(s):

Tumor Cells ◽

Circulating Tumor Cells ◽

Whole Blood ◽

In Vitro Diagnostic

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56P Single circulating tumor cells RNA profiling by label-free enrichment and active single cell selection on an integrated fluidic system

Annals of Oncology ◽

10.1016/s0923-7534(21)00216-7 ◽

2016 ◽

Vol 27 ◽

pp. ix15-ix16

Author(s):

Y.F. Lee ◽

N. Ramalingam ◽

L. Szpankowski ◽

A. Leyrat ◽

N.D. Angeles ◽

...

Keyword(s):

Single Cell ◽

Tumor Cells ◽

Circulating Tumor Cells ◽

Cell Selection ◽

Label Free ◽

Rna Profiling ◽

Free Enrichment

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Mitotic arrest affects clustering of tumor cells

10.21203/rs.3.rs-47408/v3 ◽

2021 ◽

Author(s):

Julia Bonnet ◽

Lise Rigal ◽

Odile Mondesert ◽

Renaud Morin ◽

Gaelle Corsaut ◽

...

Keyword(s):

Tumor Cells ◽

Circulating Tumor Cells ◽

Cancer Cell ◽

Cell Aggregation ◽

Metastatic Potential ◽

Mitotic Arrest ◽

Chemotherapeutic Agents ◽

The Impact ◽

Mcf 7

Abstract Background Cancer cell aggregation is a key process involved in the formation of tumor cell clusters. It has recently been shown that clusters of circulating tumor cells (CTCs) have an increased metastatic potential compared to isolated circulating tumor cells. Several widely used chemotherapeutic agents that target the cytoskeleton microtubules and cause cell cycle arrest at mitosis have been reported to modulate CTC number or the size of CTC clusters. Results In this study, we investigated in vitro the impact of mitotic arrest on the ability of breast tumor cells to form clusters. By using live imaging and quantitative image analysis, we found that MCF-7 cancer cell aggregation is compromised upon incubation with paclitaxel or vinorelbine, two chemotherapeutic drugs that target microtubules. In line with these results, we observed that MCF-7 breast cancer cells experimentally synchronized and blocked in metaphase aggregated poorly and formed loose clusters. To monitor clustering at the single-cell scale, we next developed and validated an in vitro assay based on live video-microscopy and custom-designed micro-devices. The study of cluster formation from MCF-7 cells that express the fluorescent marker LifeAct-mCherry using this new assay allowed showing that substrate anchorage-independent clustering of MCF-7 cells was associated with the formation of actin-dependent highly dynamic cell protrusions. Metaphase-synchronized and blocked cells did not display such protrusions, and formed very loose clusters that failed to compact. Conclusions Altogether, our results suggest that mitotic arrest induced by microtubule-targeting anticancer drugs prevents cancer cell clustering and therefore, could reduce the metastatic potential of circulating tumor cells.

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