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Open AccessArticle

Establishment of Novel Gastric Cancer Patient-Derived Xenografts and Cell Lines: Pathological Comparison between Primary Tumor, Patient-Derived, and Cell-Line Derived Xenografts

1
Department of Pathology and Clinical Laboratories, National Cancer Center Hospital East, Kashiwa 277-8577, Japan
2
Division of Innovative Pathology and Laboratory Medicine, EPOC, National Cancer Center, Kashiwa 277-8577, Japan
3
Division of Biomarker Discovery, EPOC, National Cancer Center, Kashiwa 277-8577, Japan
4
Department of Pathology and Clinical Laboratories, National Cancer Center Hospital, Tokyo 104-0045, Japan
5
Department of Gastric Surgery, National Cancer Center Hospital, Tokyo 104-0045, Japan
6
Department of Gastric Surgery, National Cancer Center Hospital East, Kashiwa 277-8577 Japan
7
Director, National Cancer Center Hospital East, Kashiwa 277-8577, Japan
*
Author to whom correspondence should be addressed.
Cells 2019, 8(6), 585; https://doi.org/10.3390/cells8060585
Received: 25 April 2019 / Revised: 17 May 2019 / Accepted: 11 June 2019 / Published: 14 June 2019
Patient-derived xenograft (PDX) models have been recognized as being more suitable for predicting therapeutic efficacy than cell-culture models. However, there are several limitations in applying PDX models in preclinical studies, including their availability—especially for cancers such as gastric cancer—that are not frequently encountered in Western countries. In addition, the differences in morphology between primary, PDX, and tumor cell line-derived xenograft (CDX) models have not been well established. In this study, we aimed to establish a series of gastric cancer PDXs and cell-lines from a relatively large number of gastric cancer patients. We also investigated the clinicopathological factors associated with the establishment of PDX and CDX models, and compared the histology between the primary tumor, PDX, and CDX that originated from the same patient. We engrafted 232 gastric cancer tissues into immune-deficient mice subcutaneously and successfully established 35 gastric cancer PDX models (15.1% success rate). Differentiated type adenocarcinomas (DAs, 19.4%) were more effectively established than poorly differentiated type adenocarcinomas (PDAs, 10.8%). For establishing CDXs, the success rate was less influenced by histological differentiation grade (DA vs. PDA, 12.1% vs. 9.8%). In addition, concordance of histological differentiation grade between primary tumors and PDXs was significant (p < 0.01), while concordance between primary tumors and CDXs was not. Among clinicopathological factors investigated, pathological nodal metastasis status (pN) was significantly associated with the success rate of PDX establishment. Although establishing cell lines from ascites fluid was more efficient (41.2%, 7/17) than resected tissues, it should be noted that all CDXs from ascites fluid had the PDA phenotype. In conclusion, we established 35 PDX and 32 CDX models from 249 gastric cancer patients; among them, 21 PDX/CDX models were established from the same patients. Our findings may provide helpful insights for establishing PDX and CDX models not only from gastric but from other cancer types, as well as select preclinical models for developing new therapeutics. View Full-Text
Keywords: patient-derived xenograft; cell line; gastric cancer; pathology patient-derived xenograft; cell line; gastric cancer; pathology
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Kuwata, T.; Yanagihara, K.; Iino, Y.; Komatsu, T.; Ochiai, A.; Sekine, S.; Taniguchi, H.; Katai, H.; Kinoshita, T.; Ohtsu, A. Establishment of Novel Gastric Cancer Patient-Derived Xenografts and Cell Lines: Pathological Comparison between Primary Tumor, Patient-Derived, and Cell-Line Derived Xenografts. Cells 2019, 8, 585.

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