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

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 c...

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Autores principales: Kuwata, Takeshi, Yanagihara, Kazuyoshi, Iino, Yuki, Komatsu, Teruo, Ochiai, Atsushi, Sekine, Shigeki, Taniguchi, Hirokazu, Katai, Hitoshi, Kinoshita, Takahiro, Ohtsu, Atsushi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6627523/
https://www.ncbi.nlm.nih.gov/pubmed/31207870
http://dx.doi.org/10.3390/cells8060585
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author Kuwata, Takeshi
Yanagihara, Kazuyoshi
Iino, Yuki
Komatsu, Teruo
Ochiai, Atsushi
Sekine, Shigeki
Taniguchi, Hirokazu
Katai, Hitoshi
Kinoshita, Takahiro
Ohtsu, Atsushi
author_facet Kuwata, Takeshi
Yanagihara, Kazuyoshi
Iino, Yuki
Komatsu, Teruo
Ochiai, Atsushi
Sekine, Shigeki
Taniguchi, Hirokazu
Katai, Hitoshi
Kinoshita, Takahiro
Ohtsu, Atsushi
author_sort Kuwata, Takeshi
collection PubMed
description 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.
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spelling pubmed-66275232019-07-23 Establishment of Novel Gastric Cancer Patient-Derived Xenografts and Cell Lines: Pathological Comparison between Primary Tumor, Patient-Derived, and Cell-Line Derived Xenografts Kuwata, Takeshi Yanagihara, Kazuyoshi Iino, Yuki Komatsu, Teruo Ochiai, Atsushi Sekine, Shigeki Taniguchi, Hirokazu Katai, Hitoshi Kinoshita, Takahiro Ohtsu, Atsushi Cells Article 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. MDPI 2019-06-14 /pmc/articles/PMC6627523/ /pubmed/31207870 http://dx.doi.org/10.3390/cells8060585 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Kuwata, Takeshi
Yanagihara, Kazuyoshi
Iino, Yuki
Komatsu, Teruo
Ochiai, Atsushi
Sekine, Shigeki
Taniguchi, Hirokazu
Katai, Hitoshi
Kinoshita, Takahiro
Ohtsu, Atsushi
Establishment of Novel Gastric Cancer Patient-Derived Xenografts and Cell Lines: Pathological Comparison between Primary Tumor, Patient-Derived, and Cell-Line Derived Xenografts
title Establishment of Novel Gastric Cancer Patient-Derived Xenografts and Cell Lines: Pathological Comparison between Primary Tumor, Patient-Derived, and Cell-Line Derived Xenografts
title_full Establishment of Novel Gastric Cancer Patient-Derived Xenografts and Cell Lines: Pathological Comparison between Primary Tumor, Patient-Derived, and Cell-Line Derived Xenografts
title_fullStr Establishment of Novel Gastric Cancer Patient-Derived Xenografts and Cell Lines: Pathological Comparison between Primary Tumor, Patient-Derived, and Cell-Line Derived Xenografts
title_full_unstemmed Establishment of Novel Gastric Cancer Patient-Derived Xenografts and Cell Lines: Pathological Comparison between Primary Tumor, Patient-Derived, and Cell-Line Derived Xenografts
title_short Establishment of Novel Gastric Cancer Patient-Derived Xenografts and Cell Lines: Pathological Comparison between Primary Tumor, Patient-Derived, and Cell-Line Derived Xenografts
title_sort establishment of novel gastric cancer patient-derived xenografts and cell lines: pathological comparison between primary tumor, patient-derived, and cell-line derived xenografts
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6627523/
https://www.ncbi.nlm.nih.gov/pubmed/31207870
http://dx.doi.org/10.3390/cells8060585
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