Establishment and evaluation of four different types of patient-derived xenograft models

Xiaoqian Ji; Siyu Chen; Yanwu Guo; Wende Li; Xiaolong Qi; Han Yang; Sa Xiao; Guang Fang; Jinfang Hu; Chuangyu Wen; Huanliang Liu; Zhen Han; Guangxu Deng; Qingbin Yang; Xiangling Yang; Yuting Xu; Zhihong Peng; Fengping Li; Nvlue Cai; Guoxin Li; Ren Huang

doi:10.1186/s12935-017-0497-4

Establishment and evaluation of four different types of patient-derived xenograft models

Cancer Cell Int. 2017 Dec 20:17:122. doi: 10.1186/s12935-017-0497-4. eCollection 2017.

Authors

Xiaoqian Ji^#^{1

2}, Siyu Chen^#², Yanwu Guo³, Wende Li², Xiaolong Qi⁴, Han Yang⁵, Sa Xiao^{2

6}, Guang Fang^{2

6}, Jinfang Hu², Chuangyu Wen⁷, Huanliang Liu⁷, Zhen Han⁴, Guangxu Deng⁴, Qingbin Yang⁴, Xiangling Yang⁷, Yuting Xu³, Zhihong Peng^{2

6}, Fengping Li⁴, Nvlue Cai², Guoxin Li⁴, Ren Huang²

Affiliations

¹ School of Basic Courses, Guangdong Pharmaceutical University, Guangzhou, 510006 China.
² Guangdong Laboratory Animals Monitoring Institute, Guangdong Key Laboratory Animal Lab, 11 Fengxin Road, Science City, Guangzhou, 510663 China.
³ Department of Neurosurgery, Zhujiang Hospital, Southern Medical University, Guangzhou, 510282 China.
⁴ Department of General Surgery, Nanfang Hospital, Southern Medical University, 1838 Baiyun Road North, Guangzhou, 510080 China.
⁵ Department of Thoracic Surgery, Sun Yat-Sen University Cancer Center, Guangzhou, 510030 China.
⁶ Guangdong Key Laboratory for Research and Development of Natural Drug, Guangdong Medical University, Zhanjiang, 524003 Guangdong China.
⁷ Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, Guangdong Institute of Gastroenterology and the Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510150 China.

^# Contributed equally.

Abstract

Background: Patient-derived xenografts (PDX) have a biologically stable in tumor architecture, drug responsiveness, mutational status and global gene-expression patterns. Numerous PDX models have been established to date, however their thorough characterization regarding the tumor formation and rates of tumor growth in the established models remains a challenging task. Our study aimed to provide more detailed information for establishing the PDX models successfully and effectively.

Methods: We transplanted four different types of solid tumors from 108 Chinese patients, including 21 glioblastoma (GBM), 11 lung cancers (LC), 54 gastric cancers (GC) and 21 colorectal cancers (CRC), and took tumor tissues passaged for three successive generations. Here we report the rate of tumor formation, tumor-forming times, tumor growth curves and mortality of mice in PDX model. We also report H&E staining and immunohistochemistry for HLA-A, CD45, Ki67, GFAP, and CEA protein expression between patient cancer tissues and PDX models.

Results: Tumor formation rate increased significantly in subsequent tumor generations. Also, the survival rates of GC and CRC were remarkably higher than GBM and LC. As for the time required for the formation of tumors, which reflects the tumor growth rate, indicated that tumor growth rate always increased as the generation number increased. The tumor growth curves also illustrate this law. Similarly, the survival rate of PDX mice gradually improved with the increased generation number in GC and CRC. And generally, there was more proliferation (Ki67+) in the PDX models than in the patient tumors, which was in accordance with the results of tumor growth rate. The histological findings confirm similar histological architecture and degrees of differentiation between patient cancer tissues and PDX models with statistical analysis by GraphPad Prism 5.0.

Conclusion: We established four different types of PDX models successfully, and our results add to the current understanding of the establishment of PDX models and may contribute to the extension of application of different types of PDX models.

Keywords: Colorectal cancer (CRC); Gastric cancer (GC); Glioblastoma (GBM); Lung cancer (LC); Patient derived xenograft (PDX).