Chen Jian, Ren Gang, Cai Rong, Wu Xiangru, Gui Ting, Zhao Jianxi, Li Huali, Guo Chen
Department of Radiology, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200092, People's Republic of China.
Department of Radiology, Children's Hospital of Fudan University, Shanghai 201102, People's Republic of China.
Cancer Manag Res. 2019 Aug 2;11:7317-7326. doi: 10.2147/CMAR.S206043. eCollection 2019.
Monitoring the fate of implanted cells over time in an experimental animal may provide a new way to track the metastatic process. Lymph node metastase is of extremely importance for the prognostic prediction of gastric carcinoma. The aim of this study was to assess the feasibility of magnetic resonance imaging (MRI), using micron-sized superparamagnetic iron oxide particles (MPIO), for monitoring of the fate of gastric cancer cells and detecting the migration of gastric cancer cells through the lymphatic system in a mouse model.
SGC-7901 gastric cancer cells were labeled with green fluorescent MPIO. The cells were monitored in vitro at multiple time points by staining for iron-labeled cells and by flow cytometric detection of the fluorescent MPIO. MPIO-labeled cells were implanted subcutaneously into nude mice, and cellular MRI was performed at different time points until 35 days postinjection.
The potential for retention of the iron particles in vitro was evaluated. Our results showed that the labeling and uptake efficiency of MPIO reached 90.0% after 24 hrs of incubation, and a small percentage of cells that retained MPIO could be examined until 16 days after labeling. In vivo MRI-based tracking over several weeks in mice revealed regions of signal loss in the primary tumors for up to 5 weeks. Furthermore, small regions of signal void were detected in images of the inguinal lymph nodes in three mice at day 28 postinjection or later, and histological assays confirmed the presence of iron-labeled cancer cells.
This study supports MPIO-based cell tracking is a useful tool for monitoring the fate of gastric cancer cells in mice over time, which may facilitate progress in understanding the mechanisms of early regional lymph node micrometastases.
在实验动物中随时间监测植入细胞的命运可能为追踪转移过程提供一种新方法。淋巴结转移对胃癌的预后预测极为重要。本研究的目的是评估使用微米级超顺磁性氧化铁颗粒(MPIO)的磁共振成像(MRI)在小鼠模型中监测胃癌细胞命运并检测胃癌细胞通过淋巴系统迁移的可行性。
用绿色荧光MPIO标记SGC - 7901胃癌细胞。通过对铁标记细胞进行染色和流式细胞术检测荧光MPIO,在体外多个时间点对细胞进行监测。将MPIO标记的细胞皮下植入裸鼠体内,并在注射后不同时间点进行细胞MRI检查,直至35天。
评估了铁颗粒在体外的保留潜力。我们的结果表明,孵育24小时后MPIO的标记和摄取效率达到90.0%,并且在标记后16天仍可检测到一小部分保留MPIO的细胞。在小鼠体内进行的数周MRI追踪显示,原发性肿瘤中的信号缺失区域可持续长达5周。此外,在注射后28天或更晚时,在三只小鼠腹股沟淋巴结的图像中检测到小的信号缺失区域,组织学分析证实存在铁标记的癌细胞。
本研究支持基于MPIO的细胞追踪是一种随时间监测小鼠胃癌细胞命运的有用工具,这可能有助于在理解早期区域淋巴结微转移机制方面取得进展。