Page 57 - ebook HCC

54 PROGRAMME AND ABSTRACTS GENEVA, SWITZERLAND EASL HCC SUMMIT 55
FEBRUARY 13 - 16, 2014

SIDE POPULATION ANALYSIS IDENTIFIES A
ROLE FOR LAMININ IN MODULATING THE
HUMAN HEPATIC CANCER STEM CELL NICHE

Olivier Govaere , Jasper Wouters , Michaela Petz , Kathleen van den Eynde ,
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Anke Van den broeck , Christophe Empsen , Lies Gremeaux , An Ceulemans , Results: Flow cytometric analysis showed that the CSC fraction in intrahepatic carcinomas
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Raymond Aerts , Frederik Nevens , Jacques Pirenne , Leo van Grunsven , Baki Topal , differs from 3.43% (±2.27) in K19-negative HCCs (n=7) to 9.29% (±4.42) in K19-positive
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Hugo Vankelecom , Wolfgang Mikulits , Mina Komuta , Tania Roskams 1 HCCs (n=7) and 15.43% (±13.98) in the mixed phenotype (n=4); gradually increasing
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1 Department of Imaging and Pathology, KULeuven, Leuven, Belgium, Department of with the degree of HPC features found in these carcinomas. Although certain markers
Medicine I, Medical University of Vienna, Vienna, Austria, Department of Abdominal (e.g. CXCR4, CD133, TWEAKR) identified the CSCs of specific histological subtypes, all CSC
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Surgery, KU Leuven and University Hospitals Leuve, Leuven, Department of Cell fractions showed elevated expression of KRT19, KRT7, TACSTD2, LAMC2 and MDR1.
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Biology, Vrije Universiteit Brussel, Brussels, Department of Development and LAMC2 immunoreactivity was mainly found in the cytoplasm and in the surrounding of
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Regeneration, KULeuven, Department of Hepatology, Department of Abdominal small HPC-like tumor cells. In the neighboring tissue, LAMC2 was seen as part of the
extracellular matrix surrounding the HPCs. In vitro, laminin significantly induced K19
BASIC SPEAKERS ABSTRACTS Introduction: Cancer stem cells (CSCs) are thought to be persistent in tumors due to their indicating that fewer cells underwent mitosis. Moreover, after 72h laminin coated HepG2 BASIC SPEAKERS ABSTRACTS
Transplant Surgery, KU Leuven and University Hospitals Leuve, Leuven, Belgium
expressionin HepG2 cells and reduced the number of phosphor-histone H3-positive cells,
Corresponding author’s e-mail: olivier.govaere@med.kuleuven.be
cells proved to be more resilient to doxorubicin treatment when compared to the non-
coated condition.
chemoresistance and are thought to be the cause for relapse and metastasis. Intrahepatic
Conclusions: In this study we identified a role for laminin as part of the specialized CSC
carcinomas displaying hepatic progenitor cell (HPC) features have been associated with
a poor prognosis, although it still remains unclear how CSCs relate to these different
histological subtypes. niche in maintaining and supporting ‘stemness’, e.g. quiescence and chemoresistance.
Aims: In this study we aim to characterize the CSC fraction in different histopathological
subtypes of intrahepatic carcinomas, reflecting their possible cell of origin. Moreover, we
focus on the influence of particular members of the specialized CSC niche in vitro.
Methodology: Candidate CSCs were isolated from clinical primary tissue samples
diagnosed as keratin(K)19 negative/positive hepatocellular carcinoma (HCC) or mixed
hepatocellular/cholangiocarcinoma (mixed phenotype), using the Side Population
technique. Isolated populations were processed for gene expression analysis and target
genes were validated using immunohistochemistry. HepG2 cells were grown in laminin
coated and non-coated conditions, and further analyzed for HPC/quiescence markers and
cytotoxicity sensitivity.