Establishment of novel long-term cultures from EpCAM positive and negative circulating tumour cells from patients with metastatic gastroesophageal cancer

Authors

Daniel Brungs, University of WollongongFollow
Elahe Minaei, University of WollongongFollow
Ann-Katrin Piper, University of WollongongFollow
Jay Perry, University of WollongongFollow
Ashleigh Splitt
Martin G. Carolan, University of WollongongFollow
Shantay Ryan
Xiao Wu
Stephanie Corde, University of WollongongFollow
Moeava Tehei, University of WollongongFollow
Morteza Aghmesheh, University of WollongongFollow
Kara L. Vine, University of WollongongFollow
Therese M. Becker
Marie Ranson, University of WollongongFollow

RIS ID

141157

Publication Details

Brungs, D., Minaei, E., Piper, A., Perry, J., Splitt, A., Carolan, M., Ryan, S., Wu, X., Corde Tehei, S., Tehei, M., Aghmesheh, M., Perrow, K., Becker, T. & Ranson, M. (2020). Establishment of novel long-term cultures from EpCAM positive and negative circulating tumour cells from patients with metastatic gastroesophageal cancer. Scientific Reports, 10 (1), 1-13.

Abstract

Circulating tumour cell (CTC) enumeration and profiling has been established as a valuable clinical tool in many solid malignancies. A key challenge in CTC research is the limited number of cells available for study. Ex vivo CTC culture permits expansion of these rare cell populations for detailed characterisation, functional assays including drug sensitivity testing, and investigation of the pathobiology of metastases. We report for the first time the establishment and characterisation of two continuous CTC lines from patients with gastroesophageal cancer. The two cell lines (designated UWG01CTC and UWG02CTC) demonstrated rapid tumorigenic growth in immunodeficient mice and exhibit distinct genotypic and phenotypic profiles which are consistent with the tumours of origin. UWG02CTC exhibits an EpCAM+, cytokeratin+, CD44+ phenotype, while UWG01CTC, which was derived from a patient with metastatic neuroendocrine cancer, displays an EpCAM−, weak cytokeratin phenotype, with strong expression of neuroendocrine markers. Further, the two cell lines show distinct differences in drug and radiation sensitivity which match differential cancer-associated gene expression pathways. This is strong evidence implicating EpCAM negative CTCs in metastasis. These novel, well characterised, long-term CTC cell lines from gastroesophageal cancer will facilitate ongoing research into metastasis and the discovery of therapeutic targets.