Veziant Julie, Gagnière Johan, Jouberton Elodie, Bonnin Virginie, Sauvanet Pierre, Pezet Denis, Barnich Nicolas, Miot-Noirault Elisabeth, Bonnet Mathilde
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.
World J Clin Oncol. 2016 Jun 10;7(3):293-301. doi: 10.5306/wjco.v7.i3.293.
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.
We choose to evaluate the tumor metabolic activity using a fluorodeoxyglucose analogue as 2-deoxyglucosone fluorescent probes and to correlate it with tumoral volume (mm(3)). 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.
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).
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.
利用光学成像研究与pks阳性大肠杆菌（E. coli）感染结肠上皮黏膜相关的分子或细胞机制。
我们选择使用氟脱氧葡萄糖类似物作为2-脱氧葡糖酮荧光探针来评估肿瘤代谢活性，并将其与肿瘤体积（mm³）相关联。通过生物发光（BLI）炎症探针监测测量髓过氧化物酶（MPO）活性和活性氧产生的炎症情况，并通过对肿瘤标本进行酶联免疫吸附测定（ELISA）将其与组织学检查和MPO水平相关联。在感染了pks阳性E. coli的裸鼠中的人结肠腺癌上皮细胞（HCT116）异种移植模型上验证了这两种信号的检测和定量。在模拟克罗恩病的结肠炎-CEABAC10 DSS模型中，在消化道内验证了炎症BLI信号。
使用2-脱氧葡糖酮荧光探针，我们观察到HCT116肿瘤摄取量高且具有特异性，与肿瘤体积相关（P = 0.0036）。使用靶向MPO的炎症探针，我们在pks阳性E. coli感染的HCT116异种移植组中检测到BLI信号的快速全身清除和显著增加（P < 0.005）。ELISA证实，在感染致病性大肠杆菌菌株的异种移植中，MPO水平显著更高（1556 ± 313.6对234.6 ± 121.6 ng/mL，P = 0.001）。此外，与未感染组相比，肿瘤样本的组织学检查证实pks阳性E. coli感染的HCT116肿瘤中有大量炎症细胞浸润。这些数据表明，在肿瘤生长之前，感染致病性大肠杆菌菌株会增强肿瘤中的炎症和ROS产生。此外，我们证明了在参考性结肠炎小鼠模型（CEABAC10/DSS）中对消化道内炎症进行监测是可行的。
使用BLI和荧光光学成像，我们提供了工具，以更好地理解疾病早期阶段如炎症性肠病和结直肠癌中的宿主-病原体相互作用。
