The cellular origins of Hepatocellular Carcinoma: possible role for Hedgehog pathway.

akronüüm: HEDGEHEP
algus: 2008-01-01
lõpp: 2010-12-31
 
programm: FP7 - Euroopa Liidu 7. raamprogramm
alaprogramm: PEOPLE - Marie Curie tegevused
instrument: MC-ERG - Marie Curie tegevused
projektikonkurss: FP7-PEOPLE-2007-2-2-ERG
projekti number: 208747
kestus kuudes: 36
partnerite arv: 1
 
lühikokkuvõte: The incidence of Human Hepatocellular Carcinoma (HCC) has been constantly increasing over last decades. Owing one of the highest mortality rates among cancers the HCC is resistant to the conventional cancer treatments. Therefore new approaches to treat this disease are vitally needed. The Hedgehog (HH) pathway has been recently implicated in the pathogenesis of several human cancers including those of the gastrointestinal tract. There is evidence that the HH pathway might be important in regulating the homeostasis of the liver and its deregulation might contribute to the development of the liver cancer. In the current project the involvement of the HH pathway in the liver cancer will be investigated in more detail taking advantage of transgenic animal models. The following tasks will be fulfilled: 1. Characterization of the involvement of hedgehog signaling in regulation of liver stem/progenitor pool and liver carcionogenesis. 2. The description of expression of GPR49 in normal liver and liver cancer. The effect of deletion or overexpression of this gene in liver development. 3. Investigate the possible existence of liver cancer stem cells. Characterization of GPR49 as possible marker of liver cancer stem cells. 4. Verification of the activity of known HH inhibitors on hepatic progenitor cells and possible liver cancer stem cells. The methodology involves monitoring the cellular composition of liver by means of flow cytometry and advanced imaging, evaluating the stem-cell and oncogenic potential of sorted cells by in vitro growth assays and in vivo transplantation experiments combined with lineage tracing using genetic markers. The gene expression signatures will be analyzed in the potential stem cell populations and based on these the pathways of interest will be studied in detail. This project will provide new insights into the process of cancer formation in the liver and provide new targets for therapy of one of the deadliest cancer forms.
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1 koordinaator Tartu Ülikool EE Viljar Jaks http://www.ut.ee