Book of Abstracts - Ruhr-Universität Bochum

OP-14
ISBOMC `10 5.7 – 9.7. 2010 Ruhr-Universität Bochum
Preclinical Development of Metal-Based Compounds:
Set Up of a Plastic Mouse Model
A. Bergamo, a V. Vidimar, a D. Gallo, a G. Chiaruttini, a and G. Sava *a,b
a Callerio Foundation Onlus, via A. Fleming 22-31, 34127, Trieste, Italy. b University of Trieste,
Faculty of Pharmacy, Department of Life Sciences, via L. Giorgieri 7, 34127, Trieste, Italy.
E-mail: a.bergamor@callerio.org
Nowadays the main goal of solid tumour chemotherapy is the treatment of metastases, primary cause
of death in most of the cancerous diseases. 1,2 The anti-cancer drugs currently used in the clinic have
only limited success: to achieve effective therapeutic approaches, selectivity should be improved and
the new drugs should be designed to hit targets specific of metastatic cells. This work arises from the
need to renew the screening’s system of the anti-tumour drugs employed for the treatment of solid
tumour metastases, a field still lacking of a simple, handy, and easily controllable in vitro models to be
used for evaluating and measuring specifically the potential anti-metastatic activity of active
principles. This project would contribute to match this unmet need through a biotechnological device,
born from the collaboration between the Callerio Foundation Onlus and the Department of Materials
and Natural Resources of the University of Trieste, able to mimic some physio-pathological
conditions, typical of the metastatic process. This system constitutes a “bridge” between the “classic in
vitro study” and the “classic in vivo study”; in the device the tumour cells can migrate, through a
microcircuit, from a well representing the primary tumour, to a well representing the target organ of
metastases. The model we wish to validate is the metastasis from colo-rectal cancer, a great social
impact disease in western countries, which prognosis and life time expectancy are mainly determined
from the progression of the secondary tumours to the liver, and not from the primary tumour itself. 3 In
order to recreate a metastatic colorectal tumour model, human colon adenocarcinoma HT-29 are
chosen as invasive and malignant cells, human non-malignant colon epithelial cell line HCEC is used
to mimic a normal colonic epithelial tissue, and immortalized human hepatocytes IHH to mimic the
healthy hepatic tissue. The first issue of this study is to set up the optimal environment to simulate the
physio-pathological process of metastatization and liver invasion through the development of a coculture
system in which the three cell lines grow together. In parallel the effects of three reference
drugs for the treatment of colorectal cancer (irinotecan, 5-fluorouracil and oxaliplatin), 4 are studied in
the same system. The results of theses series of experiments, propaedeutic to the extension of the coculture
model in the biotechnological device, will be presented.
Acknowledgements
This work was carried out within the framework of COST Action D39.
References
1. P. Cairns, Nat. Rev. Cancer 2006, 7, 531-543.
2. http://www.nlm.nih.gov/medlineplus/cancer.html
3. J.M. McLoughlin, E.H. Jensen, M. Malafa, Cancer Control 2006, 13, 32-41.
4. M. Koopman, C.J. Punt, Eur. J. Cancer 2009, 45 Suppl. 1, 50-56.
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