Molecular Portrait of Metastasis-Competent Circulating Tumor Cells in Colon Cancer Reveals the Crucial Role of Genes Regulating Energy Metabolism and DNA Repair

Author:

Alix-Panabières Catherine12,Cayrefourcq Laure12,Mazard Thibault34,Maudelonde Thierry52,Assenat Eric6,Assou Said78

Affiliation:

1. Laboratory of Rare Human Circulating Cells, Department of Cellular and Tissue Biopathology of Tumors, University Medical Centre, Montpellier, France

2. EA2415 – Help for Personalized Decision: Methodological Aspects, University Institute of Clinical Research (IURC), University of Montpellier, Montpellier, France

3. Department of Medical Oncology, Institut du Cancer à Montpellier (ICM), France

4. Institut du Cancer à Montpellier (ICM), Montpellier, France

5. Laboratory of Hormonal and Cell Biology, University Medical Centre, Montpellier, France

6. Department of Medical Oncology, University Medical Centre, Montpellier, France

7. University of Montpellier, UFR de Médecine, Montpellier, France

8. INSERM U1183; Institute for Regenerative Medicine and Biotherapy, CHU Montpellier, Hôpital Saint-Eloi, Montpellier, France

Abstract

AbstractBACKGROUNDUnraveling the molecular mechanisms that regulate the biology of metastasis-competent circulating tumor cells (CTCs) is urgently needed to understand metastasis formation and tumor relapse. Our group previously established the first cell line (CTC-MCC-41) derived from metastasis-competent CTCs of a patient with colon cancer.METHODSIn this study, we analyzed the transcriptome of CTC-MCC-41 cells using Human Genome U133 Plus 2.0 microarrays with the aim of unraveling the molecular basis of their special features (stem cell properties and ability to initiate and support metastasis formation).RESULTSComparison of the transcriptome data of metastasis-competent CTC-MCC-41 cells and of HT-29 cells (derived from a primary colon cancer) highlights the differential expression of genes that regulate energy metabolism [peroxisome proliferator-activated receptor γ coactivator 1A (PPARGC1A), peroxisome proliferator-activated receptor γ coactivator 1B (PPARGC1B), fatty acid binding protein 1 (FABP1), aldehyde dehydrogenase 3 family member A1 (ALDH3A1)], DNA repair [BRCA1 interacting protein C-terminal helicase 1 (BRIP1), Fanconi anemia complementation group B (FANCB), Fanconi anemia complementation group M (FANCM)], and stemness [glutaminase 2 (GLS2), cystathionine-beta-synthase (CBS), and cystathionine gamma-lyase (CTH)]. The differential expression of 20 genes was validated by quantitative reverse transcription PCR.CONCLUSIONSThis study gives a comprehensive outlook on the molecular events involved in colon cancer progression and provides potential CTC biomarkers that may help develop new therapies to specifically target CTCs with stem cell properties that cause metastases and tumor relapse in patients with colon cancer.

Funder

Direction Générale de l'offre de Soins

Roche

Amgen

Publisher

Oxford University Press (OUP)

Subject

Biochemistry (medical),Clinical Biochemistry

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