Cancer Research - Europa

• markers correlating with the immune or other defence
responses of the organism towards tumor cells.
The reason for concentrating on both classes of markers is
that interactions between developing tumors and the tumor
microenvironment are decisive for tumor survival or rejection.
Strategies to boost anti-tumor immunity have been
explored for many years. Therefore, knowledge of tumor
markers as well as defence response markers will increase
the versatility of the anti-tumor drug screening system to be
developed in the project.
Based on the genomic analyses in the project, tools will be
developed for high-throughput simultaneous quantifi cation
of defi ned subsets of relevant marker genes. Next, the
combination of high-throughput marker analysis and the
tumor cell implantation system will be applied to investigate
diff erent oncogenic cell implants and to carry out
a case study with a test panel of drugs used in human
cancer therapy. This will allow assessment of which markers
represent important factors with roles in tumor growth
and/or metastasis or roles in defence responses. Knowledge
of these factors is expected to form a solid basis for
further development of a powerful screening system that
can be off ered to the pharmaceutical industry after the
project. Furthermore, technical expertise in development
and application of high-throughput analysis tools will be
used to expand the service activities of SMEs involved in
the project and strengthen their position. Finally, basic
knowledge of disease markers, an expected achievement
of the project, is indispensable to advance biomedical
research in the zebrafi sh model.
Expected results
The strategic aim of the ZF-TOOLS project is the development
of a zebrafi sh embryo screening system as an
innovative genomics tool. This system will be employed for
high-throughput eff ectiveness testing of pharmaceutical
compounds that have the potential to infl uence disease
processes including tumor growth, metastasis and immune
defence responses. This zebrafi sh screening tool off ers some
unique features that make it very attractive in comparison
with existing tools:
• it combines the power of genomic analysis of disease
marker genes with the power of in-vivo monitoring of
SCIENTIFIC MODEL SYSTEMS
Two-day-old zebrafi sh embryo.
disease processes in a transparent vertebrate model
organism;
• it has the potential for high-throughput application due
to the small size of zebrafi sh embryos, the high numbers
with which embryos can be obtained and the choice of
high-throughput molecular screening tools that will be
developed within the project.
In order to establish the zebrafi sh screening tools, the ZF-
TOOLS project will undertake a multidisciplinary functional
genomics approach integrating diff erent global expression
profi ling techniques and bioinformatics. High-throughput
tests for expression screening of defi ned sets of newly identifi
ed disease marker genes and disease-associated small
regulatory RNAs will be developed. In addition, based on
genomic data resulting from the project, a collection of novel
oncogenic and fl uorescent reporter cell lines will be
developed, suitable for implantation into zebrafi sh embryos
and in-vivo monitoring of tumor growth and metastasis
processes. These cell lines also off er the attractive possibility
to perform complementary, in vitro cell culture based
screens. With this approach the ZF-TOOLS project is expected
to result in:
• knowledge of tumor growth and metastasis factors and
organismal defence factors;
• high-throughput tools for quantitative analysis of disease
marker sets;
• a collection of constitutive and inducible, oncogenic and
non-oncogenic reporter cell lines useful for basic disease
research and for application in screening systems;
• case study results of a novel anti-tumor drug screening
system, based on the implantation of fl uorescently labeled
tumor cells into zebrafi sh embryos.
Potential applications
The ZF-TOOLS project aims to make an impact on reinforcing
European competitiveness by generating strategic knowledge
in a multidisciplinary research approach. The studies to
be carried out within the ZF-TOOLS project will result in the
development of novel tools for biomedical research and
pharmaceutical screenings as well as in technical expertise
that will be valuable to a broad range of research topics.
These tools and technology will be exploited for basic research
of vertebrate disease as well as for strategic research and
service activities of three high-tech SMEs.
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