Published online Jun 10, 2016. doi: 10.5306/wjco.v7.i3.293
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.
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.