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

Background: 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 in
vivo models which allow the stepwise improvement of immunotherapies
for gastric cancer. Methods: 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/TagCEA) mice (mGC2(CEA), mGC4(CEA), mGC11(CEA)). 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. Results: 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 in vitro. 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(b) haplotype. Conclusion: 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.