Circulating tumour cells from patients with colorectal cancer have cancer stem cell hallmarks in ex vivo culture
Objective
Although counting of circulating tumour cells (CTC) has attracted a broad interest as potential markers of tumour progression and treatment response, the lack of functional characterisation of these cells had become a bottleneck in taking these observations to the clinic. Our objective was to culture these cells in order to understand them and exploit their therapeutic potential to the full.
Design
Here, hypothesising that some CTC potentially have cancer stem cell (CSC) phenotype, we generated several CTC lines from the blood of patients with advanced metastatic colorectal cancer (CRC) based on their self-renewal abilities. Multiple standard tests were then employed to characterise these cells.
Results
Our CTC lines self-renew, express CSC markers and have multilineage differentiation ability, both in vitro and in vivo. Patient-derived CTC lines are tumorigenic in subcutaneous xenografts and are also able to colonise the liver after intrasplenic injection. RNA sequencing analyses strikingly demonstrate that drug metabolising pathways represent the most upregulated feature among CTC lines in comparison with primary CRC cells grown under similar conditions. This result is corroborated by the high resistance of the CTC lines to conventional cytotoxic compounds.
Conclusions
Taken together, our results directly demonstrate the existence of patient-derived colorectal CTCs that bear all the functional attributes of CSCs. The CTC culture model described here is simple and takes <1 month from blood collection to drug testing, therefore, routine clinical application could facilitate access to personalised medicine.
Citation
@article{grillet2016,
author = {Fanny Grillet and Elsa Bayet and Olivia Villeronce and Luke
Zappia and Ebba Louise Lagerqvist and Sebastian Lunke and Emmanuelle
Charafe-Jauffret and Kym Pham and Christina Molck and Nathalie
Rolland and Jean François Bourgaux and Michel Prudhomme and Claire
Philippe and Sophie Bravo and Jean Christophe Boyer and Lucile
Canterel-Thouennon and Graham Roy Taylor and Arthur Hsu and Jean
Marc Pascussi and Frédéric Hollande and Julie Pannequin},
title = {Circulating Tumour Cells from Patients with Colorectal Cancer
Have Cancer Stem Cell Hallmarks in Ex Vivo Culture},
journal = {Gut},
date = {2016-07-01},
url = {https://lazappi.id.au/publications/2016-grillet-colorectal-CTCs},
doi = {10.1136/gutjnl-2016-311447},
issn = {0017-5749, 1468-3288},
langid = {en},
abstract = {**Objective** Although counting of circulating tumour
cells (CTC) has attracted a broad interest as potential markers of
tumour progression and treatment response, the lack of functional
characterisation of these cells had become a bottleneck in taking
these observations to the clinic. Our objective was to culture these
cells in order to understand them and exploit their therapeutic
potential to the full. **Design** Here, hypothesising that some CTC
potentially have cancer stem cell (CSC) phenotype, we generated
several CTC lines from the blood of patients with advanced
metastatic colorectal cancer (CRC) based on their self-renewal
abilities. Multiple standard tests were then employed to
characterise these cells. **Results** Our CTC lines self-renew,
express CSC markers and have multilineage differentiation ability,
both in vitro and in vivo. Patient-derived CTC lines are tumorigenic
in subcutaneous xenografts and are also able to colonise the liver
after intrasplenic injection. RNA sequencing analyses strikingly
demonstrate that drug metabolising pathways represent the most
upregulated feature among CTC lines in comparison with primary CRC
cells grown under similar conditions. This result is corroborated by
the high resistance of the CTC lines to conventional cytotoxic
compounds. **Conclusions** Taken together, our results directly
demonstrate the existence of patient-derived colorectal CTCs that
bear all the functional attributes of CSCs. The CTC culture model
described here is simple and takes \textless1 month from blood
collection to drug testing, therefore, routine clinical application
could facilitate access to personalised medicine.}
}