Basic Study
Copyright ©The Author(s) 2016. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Clin Oncol. Jun 10, 2016; 7(3): 293-301
Published online Jun 10, 2016. doi: 10.5306/wjco.v7.i3.293
Association of colorectal cancer with pathogenic Escherichia coli: Focus on mechanisms using optical imaging
Julie Veziant, Johan Gagnière, Elodie Jouberton, Virginie Bonnin, Pierre Sauvanet, Denis Pezet, Nicolas Barnich, Elisabeth Miot-Noirault, Mathilde Bonnet
Julie Veziant, Johan Gagnière, Virginie Bonnin, Pierre Sauvanet, Denis Pezet, Nicolas Barnich, Mathilde Bonnet, UMR1071 Inserm/Université d’Auvergne and INRA USC2018, Clermont Université, 63000 Clermont-Ferrand, France
Julie Veziant, Johan Gagnière, Pierre Sauvanet, Denis Pezet, Service de Chirurgie Digestive, Centre Hospitalier Universitaire, 63000 Clermont Ferrand, France
Elodie Jouberton, Elisabeth Miot-Noirault, UMR990 Inserm/Université d’Auvergne, Clermont Université, 63000 Clermont-Ferrand, France
Elodie Jouberton, Service de Médecine Nucléaire, Centre Jean Perrin, 63000 Clermont Ferrand, France
Author contributions: Veziant J, Gagnière J, Bonnet M conceived and designed the study, analyzed data and drafted the manuscript; Veziant J, Jouberton E, Bonnin V, Bonnet M performed experiments and analyses; Miot-Noirault E contributed to imaging platform management; Sauvanet P performed histological technics; Gagnière J, Pezet D, Barnich N, Miot-Noirault E and Bonnet M contributed to critical comments and revised the manuscript; all authors read, contributed to, and approved the final manuscript.
Supported by Veziant J was supported by «année-recherche» grants from the Ministère de la Santé and the Faculté de Médecine de Clermont-Ferrand; Gagnière J was supported by a “Nuovo Soldati Foundation for Cancer Research” grant.
Institutional review board statement: Not concerned.
Institutional animal care and use committee statement: The studies were performed in accordance with the French Regional Ethical Animal Use Committee (No. CEEA-02).
Conflict-of-interest statement: No.
Data sharing statement: Not concerned.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
Correspondence to: Dr. Mathilde Bonnet, PhD, UMR1071 Inserm/Université d’Auvergne and INRA USC2018, Clermont Université, 28 Place Henri Dunant, 63000 Clermont-Ferrand, France.
Telephone: +33-4-73178381 Fax: +33-4-73178381
Received: June 24, 2015
Peer-review started: June 28, 2015
First decision: October 8, 2015
Revised: February 29, 2016
Accepted: March 24, 2016
Article in press: March 25, 2016
Published online: June 10, 2016

AIM: To investigate the molecular or cellular mechanisms related to the infection of epithelial colonic mucosa by pks-positive Escherichia coli (E. coli) using optical imaging.

METHODS: We choose to evaluate the tumor metabolic activity using a fluorodeoxyglucose analogue as 2-deoxyglucosone fluorescent probes and to correlate it with tumoral volume (mm3). Inflammation measuring myeloperoxidase (MPO) activity and reactive oxygen species production was monitored by a bioluminescent (BLI) inflammation probe and related to histological examination and MPO levels by enzyme-linked immunosorbent assay (ELISA) on tumor specimens. The detection and quantitation of these two signals were validated on a xenograft model of human colon adenocarcinoma epithelial cells (HCT116) in nude mice infected with a pks-positive E. coli. The inflammatory BLI signal was validated intra-digestively in the colitis-CEABAC10 DSS models, which mimicked Crohn’s disease.

RESULTS: Using a 2-deoxyglucosone fluorescent probe, we observed a high and specific HCT116 tumor uptake in correlation with tumoral volume (P = 0.0036). Using the inflammation probe targeting MPO, we detected a rapid systemic elimination and a significant increase of the BLI signal in the pks-positive E. coli-infected HCT116 xenograft group (P < 0.005). ELISA confirmed that MPO levels were significantly higher (1556 ± 313.6 vs 234.6 ± 121.6 ng/mL P = 0.001) in xenografts infected with the pathogenic E. coli strain. Moreover, histological examination of tumor samples confirmed massive infiltration of pks-positive E. coli-infected HCT116 tumors by inflammatory cells compared to the uninfected group. These data showed that infection with the pathogenic E. coli strain enhanced inflammation and ROS production in tumors before tumor growth. Moreover, we demonstrated that the intra-digestive monitoring of inflammation is feasible in a reference colitis murine model (CEABAC10/DSS).

CONCLUSION: Using BLI and fluorescence optical imaging, we provided tools to better understand host-pathogen interactions at the early stage of disease, such as inflammatory bowel disease and colorectal cancer.

Keywords: Colorectal carcinoma, Escherichia coli, Colibactin, Myeloperoxidase, In vivo optical imaging

Core tip: Approximately 15% of cancers are related to infectious agents. Colorectal cancer (CRC) is thus a complex association of non-neoplastic and tumoral cells and a large amount of microorganisms. Recent studies reported that pks-positive Escherichia coli (E. coli) strains are more frequently detected in CRC, suggesting their possible role in tumor development. Optical imaging has emerged as a powerful tool in translational cancer research, providing new possibilities for the spatiotemporal monitoring of carcinogenesis in mouse models. It may be particularly helpful in better understanding the in vivo host-pathogen-interactions in tumor development. This is the first study to use optical imaging to explore CRC carcinogenesis and associated pathogenic E. coli.