Abstract

Liquid Biopsy in Cancer Patients: A focus on Metastasis-Initiator Circulating Tumor Cells

Catherine Alix-Panabieres, Associate Professor, University Medical Center of Montpellier

Circulating tumor cells (CTCs) in blood are promising new biomarkers potentially useful for prognostic prediction and monitoring of therapies in patients with solid tumors including colon cancer. Moreover, CTC research opens a new avenue for understanding the biology of metastasis in cancer patients. However, an in-depth investigation of CTCs is hampered by the very low number of these cells, especially in the blood of colorectal cancer patients. Thus, the establishment of cell cultures and permanent cell lines from CTCs has become the most challenging task over the past year.

We described, for the first time, the establishment of cell cultures and a permanent cell line from CTCs of one colon cancer patient (Cayrefourcq et al.Cancer Res. 2015). The cell line designated CTC-MCC-41 is in culture for more than three years and has been characterized at the genome, transcriptome, proteome and secretome levels. This thorough analysis showed that CTC-MCC-41 cells resemble characteristics of the original tumor cells in the colon cancer patient and display a stable phenotype characterized by an intermediate epithelial/mesenchymal phenotype, stem-cell like properties and an osteomimetic signature indicating a bone marrow origin. Functional studies showed that CTC-MCC-41 cells induced rapidly in vitroendothelial cell tube formation and in vivotumors after xenografting in immunodeficient mice. In 2017, we defined the molecular portrait of these metastasis-competent CTCs (Alix-Panabières et al. Clin Chem. 2017). These results highlight that CTC-MCC-41 line display a very specific transcription program completely different than those of the primary and metastatic colon cancer cell lines.More recently, we characterized 8 additional CTC lines using blood samples from the same metastatic cancer: a unique biological material collected before and after chemotherapy and targeted therapy, and during cancer progression (Soler et al. Sci. Rep. 2018).

Such data may supply insights for the discovery of new biomarkers to identify the most aggressive CTC sub-populations and for the development of new drugs to inhibit metastasis-initiator CTCs in colon cancer.