Characterization of gastric adenocarcinoma cell lines established from CEA424/<it>SV40 T antigen</it>-transgenic mice with or without a human <it>CEA </it>transgene

<p>Abstract</p> <p>Background</p> <p>Gastric carcinoma is one of the most frequent cancers worldwide. Patients with gastric cancer at an advanced disease stage have a poor prognosis, due to the limited efficacy of available therapies. Therefore, the development of new t...

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Main Authors: Hatz Rudolf A, Winter Hauke, van den Engel Natasja K, Nöckel Jessica, Zimmermann Wolfgang, Kammerer Robert
Format: Article
Language:English
Published: BMC 2006-03-01
Series:BMC Cancer
Online Access:http://www.biomedcentral.com/1471-2407/6/57
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author Hatz Rudolf A
Winter Hauke
van den Engel Natasja K
Nöckel Jessica
Zimmermann Wolfgang
Kammerer Robert
author_facet Hatz Rudolf A
Winter Hauke
van den Engel Natasja K
Nöckel Jessica
Zimmermann Wolfgang
Kammerer Robert
author_sort Hatz Rudolf A
collection DOAJ
description <p>Abstract</p> <p>Background</p> <p>Gastric carcinoma is one of the most frequent cancers worldwide. Patients with gastric cancer at an advanced disease stage have a poor prognosis, due to the limited efficacy of available therapies. Therefore, the development of new therapies, like immunotherapy for the treatment of gastric cancer is of utmost importance. Since the usability of existing preclinical models for the evaluation of immunotherapies for gastric adenocarcinomas is limited, the goal of the present study was to establish murine <it>in vivo </it>models which allow the stepwise improvement of immunotherapies for gastric cancer.</p> <p>Methods</p> <p>Since no murine gastric adenocarcinoma cell lines are available we established four cell lines (424GC, mGC3, mGC5, mGC8) from spontaneously developing tumors of CEA424/SV40 T antigen (CEA424/Tag) mice and three cell lines derived from double-transgenic offsprings of CEA424/Tag mice mated with human carcinoembryonic antigen (CEA)-transgenic (CEA424/Tag-CEA) mice (mGC2<sup>CEA</sup>, mGC4<sup>CEA</sup>, mGC11<sup>CEA</sup>). CEA424/Tag is a transgenic C57BL/6 mouse strain harboring the Tag under the control of a -424/-8 bp CEA gene promoter which leads to the development of invasive adenocarcinoma in the glandular stomach. Tumor cell lines established from CEA424/Tag-CEA mice express the well defined tumor antigen CEA under the control of its natural regulatory elements.</p> <p>Results</p> <p>The epithelial origin of the tumor cells was proven by morphological criteria including the presence of mucin within the cells and the expression of the cell adhesion molecules EpCAM and CEACAM1. All cell lines consistently express the transgenes CEA and/or Tag and MHC class I molecules leading to their susceptibility to lysis by Tag-specific CTL <it>in vitro</it>. Despite the presentation of CTL-epitopes derived from the transgene products the tumor cell lines were tumorigenic when grafted into C57BL/6, CEA424/Tag or CEA424/Tag-CEA-transgenic hosts and no significant differences in tumor take and tumor growth were observed in the different hosts. Although no spontaneous tumor rejection was observed, vaccination of C57BL/6 mice with lysates from gastric carcinoma cell lines protected C57BL/6 mice from tumor challenge, demonstrating the tumorigenicity of the tumor cell lines in nontransgenic mice of the H-2<sup>b </sup>haplotype.</p> <p>Conclusion</p> <p>These tumor cell lines grafted in different syngeneic hosts should prove to be very useful to optimize immunotherapy regimens to be finally tested in transgenic animals developing primary gastric carcinomas.</p>
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spelling doaj.art-a2754a713b374af28c67160093a7ce092022-12-21T18:27:48ZengBMCBMC Cancer1471-24072006-03-01615710.1186/1471-2407-6-57Characterization of gastric adenocarcinoma cell lines established from CEA424/<it>SV40 T antigen</it>-transgenic mice with or without a human <it>CEA </it>transgeneHatz Rudolf AWinter Haukevan den Engel Natasja KNöckel JessicaZimmermann WolfgangKammerer Robert<p>Abstract</p> <p>Background</p> <p>Gastric carcinoma is one of the most frequent cancers worldwide. Patients with gastric cancer at an advanced disease stage have a poor prognosis, due to the limited efficacy of available therapies. Therefore, the development of new therapies, like immunotherapy for the treatment of gastric cancer is of utmost importance. Since the usability of existing preclinical models for the evaluation of immunotherapies for gastric adenocarcinomas is limited, the goal of the present study was to establish murine <it>in vivo </it>models which allow the stepwise improvement of immunotherapies for gastric cancer.</p> <p>Methods</p> <p>Since no murine gastric adenocarcinoma cell lines are available we established four cell lines (424GC, mGC3, mGC5, mGC8) from spontaneously developing tumors of CEA424/SV40 T antigen (CEA424/Tag) mice and three cell lines derived from double-transgenic offsprings of CEA424/Tag mice mated with human carcinoembryonic antigen (CEA)-transgenic (CEA424/Tag-CEA) mice (mGC2<sup>CEA</sup>, mGC4<sup>CEA</sup>, mGC11<sup>CEA</sup>). CEA424/Tag is a transgenic C57BL/6 mouse strain harboring the Tag under the control of a -424/-8 bp CEA gene promoter which leads to the development of invasive adenocarcinoma in the glandular stomach. Tumor cell lines established from CEA424/Tag-CEA mice express the well defined tumor antigen CEA under the control of its natural regulatory elements.</p> <p>Results</p> <p>The epithelial origin of the tumor cells was proven by morphological criteria including the presence of mucin within the cells and the expression of the cell adhesion molecules EpCAM and CEACAM1. All cell lines consistently express the transgenes CEA and/or Tag and MHC class I molecules leading to their susceptibility to lysis by Tag-specific CTL <it>in vitro</it>. Despite the presentation of CTL-epitopes derived from the transgene products the tumor cell lines were tumorigenic when grafted into C57BL/6, CEA424/Tag or CEA424/Tag-CEA-transgenic hosts and no significant differences in tumor take and tumor growth were observed in the different hosts. Although no spontaneous tumor rejection was observed, vaccination of C57BL/6 mice with lysates from gastric carcinoma cell lines protected C57BL/6 mice from tumor challenge, demonstrating the tumorigenicity of the tumor cell lines in nontransgenic mice of the H-2<sup>b </sup>haplotype.</p> <p>Conclusion</p> <p>These tumor cell lines grafted in different syngeneic hosts should prove to be very useful to optimize immunotherapy regimens to be finally tested in transgenic animals developing primary gastric carcinomas.</p>http://www.biomedcentral.com/1471-2407/6/57
spellingShingle Hatz Rudolf A
Winter Hauke
van den Engel Natasja K
Nöckel Jessica
Zimmermann Wolfgang
Kammerer Robert
Characterization of gastric adenocarcinoma cell lines established from CEA424/<it>SV40 T antigen</it>-transgenic mice with or without a human <it>CEA </it>transgene
BMC Cancer
title Characterization of gastric adenocarcinoma cell lines established from CEA424/<it>SV40 T antigen</it>-transgenic mice with or without a human <it>CEA </it>transgene
title_full Characterization of gastric adenocarcinoma cell lines established from CEA424/<it>SV40 T antigen</it>-transgenic mice with or without a human <it>CEA </it>transgene
title_fullStr Characterization of gastric adenocarcinoma cell lines established from CEA424/<it>SV40 T antigen</it>-transgenic mice with or without a human <it>CEA </it>transgene
title_full_unstemmed Characterization of gastric adenocarcinoma cell lines established from CEA424/<it>SV40 T antigen</it>-transgenic mice with or without a human <it>CEA </it>transgene
title_short Characterization of gastric adenocarcinoma cell lines established from CEA424/<it>SV40 T antigen</it>-transgenic mice with or without a human <it>CEA </it>transgene
title_sort characterization of gastric adenocarcinoma cell lines established from cea424 it sv40 t antigen it transgenic mice with or without a human it cea it transgene
url http://www.biomedcentral.com/1471-2407/6/57
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