Hassan Md Sazzad, Awasthi Niranjan, Li Jun, Schwarz Margaret A, Schwarz Roderich E, von Holzen Urs
Department of Surgery, Indiana University School of Medicine, South Bend, IN, United States of America.
Harper Cancer Research Institute, South Bend, IN, United States of America.
PLoS One. 2017 Feb 22;12(2):e0171824. doi: 10.1371/journal.pone.0171824. eCollection 2017.
Esophageal adenocarcinoma (EAC) has become the dominant type of esophageal cancer in United States. The 5-year survival rate of EAC is below 20% and most patients present with locally advanced or widespread metastatic disease, where current treatment is largely ineffective. Therefore, new therapeutic approaches are urgently needed. Improvement of EAC patient outcome requires well-characterized animal models in which to evaluate novel therapeutics. In this study we aimed to establish a peritoneal dissemination xenograft mouse model of EAC that would support survival outcome analyses. To find the best candidate cell line from 7 human EAC cell lines of different origin named ESO26, OE33, ESO51, SK-GT-2, OE19, OACM5.1C and Flo-1 were injected intraperitoneally/subcutaneously into SCID mice. The peritoneal/xenograft tumor formation and mouse survival were compared among different groups. All cell lines injected subcutaneously formed tumors within 3 months at variable rates. All cell lines except OACM5.1C formed intraperitoneal tumors within 3 months at variable rates. Median animal survival with peritoneal dissemination was 108 days for ESO26 cells (5X106), 65 days for OE33 cells (5X106), 88 days for ESO51 cells (5X106), 76 days for SK-GT-2 cells (5X106), 55 days for OE19 cells (5X106), 45 days for OE19 cells (10X106) and 82 days for Flo-1 cells (5X106). Interestingly, only in the OE19 model all mice (7/7 for 5X106 and 5/5 for10X106) developed bloody ascites with liver metastasis after intraperitoneal injection. The median survival time of these animals was the shortest (45 days for 10X106 cells). In addition, median survival was significantly increased after paclitaxel treatment compared with the control group (57 days versus 45 days, p = 0.0034) along with a significant decrease of the relative subcutaneous tumor volume (p = 0.00011). Thus peritoneal dissemination mouse xenograft model for survival outcome assessment after intraperitoneal injection of OE19 cells will be very useful for the evaluation of cancer therapeutics.
食管腺癌（EAC）已成为美国食管癌的主要类型。EAC的5年生存率低于20%，大多数患者就诊时已处于局部晚期或广泛转移阶段，目前的治疗方法大多无效。因此，迫切需要新的治疗方法。改善EAC患者的预后需要特征明确的动物模型来评估新的治疗方法。在本研究中，我们旨在建立一种EAC的腹膜播散异种移植小鼠模型，以支持生存结果分析。为了从7种不同来源的人EAC细胞系（ESO26、OE33、ESO51、SK-GT-2、OE19、OACM5.1C和Flo-1）中找到最佳候选细胞系，将其腹腔内/皮下注射到SCID小鼠体内。比较不同组之间的腹膜/异种移植肿瘤形成情况和小鼠存活率。所有皮下注射的细胞系在3个月内均以不同速率形成肿瘤。除OACM5.1C外，所有细胞系在3个月内均以不同速率形成腹腔内肿瘤。ESO26细胞（5×10⁶）腹腔播散后的动物中位生存期为108天，OE33细胞（5×10⁶）为65天，ESO51细胞（5×10⁶）为88天，SK-GT-2细胞（5×10⁶）为76天，OE19细胞（5×10⁶）为55天，OE19细胞（10×10⁶）为45天，Flo-1细胞（5×10⁶）为82天。有趣的是，只有在OE19模型中，所有小鼠（5×10⁶组7/7，10×10⁶组5/5）腹腔注射后均出现血性腹水并伴有肝转移。这些动物的中位生存时间最短（10×10⁶细胞组为45天）。此外，与对照组相比，紫杉醇治疗后中位生存期显著延长（57天对45天，p = 0.0034），同时相对皮下肿瘤体积显著减小（p = 0.00011）。因此，腹腔注射OE19细胞后用于生存结果评估的腹膜播散小鼠异种移植模型对于癌症治疗的评估将非常有用。
