Establishing metastatic patient-derived xenograft model for colorectal cancer.
Establishing metastatic patient-derived xenograft model for colorectal cancer.
复制标题
建立转移性结直肠癌患者来源的异种移植模型。
DOI：
10.1093/jjco/hyaa089
复制
发表时间：
2020
影响因子：
2.4
通讯作者：
W. Xu
中科院分区：
文献类型：
--
作者：
Yanmei Zhang;S. Lee;Cheng Wang;Yunhe Gao;Jiyang Li;W. Xu
背景
患者来源的异种移植模型是药物发现和癌症生物学研究的有力工具。以往的转移性结直肠癌模型由于成功率低、转移时间长而限制了其应用。因此，在这项研究中，我们的目的是描述一个优化的协议，更快地建立结直肠癌转移患者来源的异种移植小鼠模型。
方法
将与Matrigel混合的较小微组织（直径约150 μm）皮下移植到NSG小鼠中，以产生第1代（P1）患者源性异种移植物。然后将来自P1患者来源的异种移植物的微肿瘤切除并原位异种移植到另一批NSG小鼠中，以产生转移性结肠直肠癌患者来源的异种移植物P2。采用苏木精-伊红染色和免疫组织化学染色比较患者来源的异种移植瘤和原发性肿瘤的特征。
结果
在18个P1异种移植模型中，约有16个成功生长肿瘤，持续50.8 ± 5.1天（成功率89.9%）。来自转移性患者的8个P1异种移植物模型中有6个在NSG接受者中成功地在结肠中生长肿瘤并转移到肝脏或肺60.9 ± 4.5天（成功率75%）。P1和P2异种移植物的组织学检查与原始患者肿瘤的组织学结构非常相似。免疫组织化学分析显示，与原始患者的肿瘤相比，生物标志物表达水平相似，包括CDH 17、Ki-67、活性β-连环蛋白、Ki-67和α平滑肌肌动蛋白。支持患者来源的异种移植肿瘤生长的基质组分是鼠源性的。
结论
转移患者来源的异种移植瘤小鼠模型建立时间短，成功率高。尽管患者来源的异种移植肿瘤得到了鼠源性基质细胞的支持，但它们保留了原始患者肿瘤的主要特征。
BACKGROUND
Patient-derived xenograft model is a powerful and promising tool for drug discovery and cancer biology studies. The application of previous metastatic colorectal cancer models has been greatly limited by its low success rate and long time to develop metastasis. Therefore, in this study, we aim to describe an optimized protocol for faster establishment of colorectal cancer metastatic patient-derived xenograft mouse models.
METHODS
Smaller micro tissues (˂150 μm in diameter) mixed with Matrigel were engrafted subcutaneously into NSG mice to generate the passage 1 (P1) patient-derived xenograft. The micro tumours from P1 patient-derived xenograft were then excised and orthotopically xenografted into another batch of NSG mice to generate a metastatic colorectal cancer patient-derived xenograft, P2. Haematoxylin and eosin and immunohistochemistry staining were performed to compare the characters between patient-derived xenograft tumours and primary tumours.
RESULTS
About 16 out of 18 P1 xenograft models successfully grew a tumour for 50.8 ± 5.1 days (success rate 89.9%). Six out of eight P1 xenograft models originating from metastatic patients successfully grew tumours in the colon and metastasized to liver or lung in the NSG recipients for 60.9 ± 4.5 days (success rate 75%). Histological examination of both P1 and P2 xenografts closely resembled the histological architecture of the original patients' tumours. Immunohistochemical analysis revealed similar biomarker expression levels, including CDH17, Ki-67, active β-catenin, Ki-67 and α smooth muscle actin when compared with the original patients' tumours. The stromal components that support the growth of patient-derived xenograft tumours were of murine origin.
CONCLUSIONS
Metastatic patient-derived xenograft mouse model could be established with shorter time and higher success rate. Although the patient-derived xenograft tumours were supported by the stromal cells of murine origin, they retained the dominant characters of the original patient tumours.
DOI：
10.1016/j.jss.2015.04.030
发表时间：
2015-11
期刊：
The Journal of surgical research
影响因子：
--
作者：
Terracina KP;Aoyagi T;Huang WC;Nagahashi M;Yamada A;Aoki K;Takabe K
通讯作者：
Takabe K
影响因子：
28.2
作者：
Kavuri SM;Jain N;Galimi F;Cottino F;Leto SM;Migliardi G;Searleman AC;Shen W;Monsey J;Trusolino L;Jacobs SA;Bertotti A;Bose R
通讯作者：
Bose R