Page 95 - ebook HCC

PROGRAMME AND ABSTRACTSAND ABSTRACTS
GENEVA, SWITZERLANDA, SWITZERLAND
EASL HCC SUMMITHCC SUMMIT
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92 PROGRAMME GENEV EASL 93
92
FEBRUAR
FEBRUARY 13 - 16, 2014Y 13 - 16, 2014
Poster Board Number B3
THE ROLE OF HYPOXIA ON LIVER PROGENITOR
CELL ACTIVATION IN A MOUSE MODEL FOR
HEPATOCELLULAR CARCINOMA

Eliene Bogaerts , Aurelie Comhaire , Femke Heindryckx , Annelies Paridaens , Results: qPCR analysis revealed an increase in cytokeratin (CK) 7, CK19 and CD44
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Yves-Paul Vandewynckel , Peter Carmeliet , Anja Geerts , Hans Van Vlierberghe 1 expression after 30w in all DEN-treated groups compared to control mice (p<0,05). In
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1 Gastro-enterology and hepatology, Ghent university, Ghent, Belgium, Department PHD2+/- mice, CK7 and CK19 mRNA concentrations increased drastically compared to
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of Medical Biochemistry and Microbiology, uppsala university, Uppsala, Sweden, WT mice after 20 weeks (p<0,01) but dropped back to WT levels after 25 weeks. For
3 Laboratory of Angiogenesis and Neurovascular link, CD44, no significant difference between PHD2+/- and WT groups could be marked.
Vesalius Research Center VIB - KU Leuven, Leuven, Belgium However, IHC for CD44 showed increased expression with longer induction and was
higher in PHD2+/- compared to WTs, significant after 30 weeks (p<0,001) and compared
Corresponding author’s e-mail: eliene.bogaerts@gmail.com to healthy controls (p<0,001).
Conclusions: During DEN-induction, LPCs are possibly in a proliferating state, as seen
Introduction: Hepatocellular carcinoma (HCC) is the 5th most common cancer worldwide by the increased levels of CK7 and CK19 and CD44 in WT and PHD+/- mice.
and is often detected in an advanced state. Current treatment options are mostly based Increased CK7, CK19 and CD44 expression in early PHD2 tumors demonstrates
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on depriving the tumor from its oxygen and nutrient supply by decreasing angiogenesis,
that activation of HIF-pathway probably influences LPC proliferation and differentiation
BASIC POSTER ABSTRACTS (LPC)-niche, creating a more aggressive tumor phenotype. Understanding more about like phenotype. This could contribute to the development of more aggressive tumors with BASIC POSTER ABSTRACTS
mostly in earlier stages of primary liver tumors, pushing them towards a more stem cell
thus creating hypoxic conditions. This could lead to an alteration in the liver progenitor cell
the influence of oxygen deprivation on progenitor cells and their differentiation is of vast
worse prognosis and has repercussions on patients receiving long term anti-angiogenic
importance when using and improving the use of hypoxia inducing therapies.
treatment.
In a previous study, we have shown that weekly injections with diethylnitrosamine (DEN)
in prolyl hydroxylase domain 2, haplodeficient (PHD2+/-) mice -who have increased HIF
stabilization (mimicking hypoxic signaling)- induces a mixed cholangiohepatocellular
carcinoma, an LPC-derived tumor, while wild type (WT) mice develop only HCC.
Aims: To assess the effect of increased hypoxia inducible factor (HIF) stabilization on LPC
activation and differentiation in a DEN induced HCC mouse model, by using PHD2 mice.
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Methodology: HCC was induced in WT and PHD2 mice by weekly DEN-injections and
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euthanized after 20, 25 and 30 weeks. RT-qPCR analysis and Immunohistochemical
staining (IHC) for LPC markers was performed.