Autologous cell lines from circulating colon cancer cells captured from sequential liquid biopsies as model to study therapy-driven tumor changes

Alexandra Soler,Said Assou,Eric Assenat,Klaus Pantel,Catherine Alix-Panabières,Pierre-Jean Lamy,Laure Cayrefourcq,Thibault Mazard,Anna Babayan

doi:10.1038/s41598-018-34365-z

Abstract

Circulating tumor cells (CTCs) are important clinical indicators for prognosis and treatment efficacy. However, CTC investigation is hampered by their low number, making the establishment of permanent CTC lines very challenging. We derived and characterized nine CTC lines using blood samples from a patient with metastatic colorectal cancer collected before and after chemotherapy and targeted therapy, and during cancer progression. These cell lines displayed an intermediate epithelial/mesenchymal phenotype, stem-cell like characteristics, angiogenesis potential, an osteomimetic signature and the capacity to escape from the immune system. Moreover, they showed changes in mRNA and protein expression (e.g., DEFA6, ABCB1 and GAL), whereas analysis of chromosomal copy number aberrations revealed no significant variation over time. These data indicate that although CTC lines derived from sequential blood samples during therapy have common traits, treatment-resistant CTC clones with distinct phenotypic characteristics are selected over time.

Highlights

Over the past years, liquid biopsy of circulating tumor cells (CTC) has received major attention as a strategy to obtain real time diagnostic and prognostic information[1,2]
In 2015, our group published the first experimental proof that a stable colon CTC line (CTC-MCC-41) could be established from CTCs isolated from the blood of a patient with metastatic colon cancer[13]
The present study provides the characterization of the other eight CTC lines derived from CTCs isolated from the same patient at different times during his follow-up before/after treatment and disease progression

Summary

Introduction

Liquid biopsy of circulating tumor cells (CTC) has received major attention as a strategy to obtain real time diagnostic and prognostic information[1,2]. We previously described the first permanent cell line (CTC-MCC-41) from circulating colon cancer cells[13]. In addition to its capacity to expand in vitro for more than 4 years, the CTC-MCC-41 cell line shows specific stem-cell like characteristics and shares some features of the original primary tumor and lymph node metastasis[13]. We established another eight CTC lines from blood samples collected from the same patient at different time points during his follow-up. Comparison of all nine autologous CTC lines (the previously described CTC-MCC-41 line and the eight new lines) highlighted their common features and main differences acquired over time

Methods

Results

Conclusion