Abstract
Hepatocellular carcinomas are devastating cancers with high mortality rates. Major risk factors are chronic hepatitis and associated cirrhosis as consequence of viral hepatitis infections, chronically ethanol consumption or metabolic disorders. While the stepwise development of liver cancer is well investigated, the role of mesenchymal cells in this process is largely unknown. To analyse epithelial-mesenchymal interactions in advanced stages of hepatocarcinogenesis, we established new cell lines from human hepatocellular carcinomas and obtained several hepatocarcinoma (HCC)-, B-lymphoblastoid (BLC)- and myofibroblastoid (MF)-lines. BLC- and MF-supernatants were able to increase DNA replication of premalignant hepatocytes. Supernatants of MF-lines enhanced angiogenesis and increased migration of HCC-lines. Besides these pro-tumourigenic effects we could also observe tumouricidal properties of mesenchymal cells, as BLC-supernatants induced cell death of HCC-lines. Linoleic acid is an important source for hydroperoxides, which may be generated either endogenously in the course of inflammation or exogenously during food processing. We found that linoleic acid hydroperoxides (=LOOH) were able to activate mesenchymal cells of the liver resulting in the release of pro-inflammatory cytokines and growth factors including TNF-alpha (=tumour necrosis factor alpha) and HB-EGF (=heparin-binding epidermal growth factor-like growth factor), which turned out to be a growth factor for premalignant hepatocytes. Furthermore LOOH enhanced the
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Citation Formats
Sagmeister, S.
Epithelial-mesenchymal interactions in early and late hepatocarcinogenesis with focus on the role of linoleic acid and its hydroperoxides.
Austria: N. p.,
2009.
Web.
Sagmeister, S.
Epithelial-mesenchymal interactions in early and late hepatocarcinogenesis with focus on the role of linoleic acid and its hydroperoxides.
Austria.
Sagmeister, S.
2009.
"Epithelial-mesenchymal interactions in early and late hepatocarcinogenesis with focus on the role of linoleic acid and its hydroperoxides."
Austria.
@misc{etde_21575255,
title = {Epithelial-mesenchymal interactions in early and late hepatocarcinogenesis with focus on the role of linoleic acid and its hydroperoxides}
author = {Sagmeister, S}
abstractNote = {Hepatocellular carcinomas are devastating cancers with high mortality rates. Major risk factors are chronic hepatitis and associated cirrhosis as consequence of viral hepatitis infections, chronically ethanol consumption or metabolic disorders. While the stepwise development of liver cancer is well investigated, the role of mesenchymal cells in this process is largely unknown. To analyse epithelial-mesenchymal interactions in advanced stages of hepatocarcinogenesis, we established new cell lines from human hepatocellular carcinomas and obtained several hepatocarcinoma (HCC)-, B-lymphoblastoid (BLC)- and myofibroblastoid (MF)-lines. BLC- and MF-supernatants were able to increase DNA replication of premalignant hepatocytes. Supernatants of MF-lines enhanced angiogenesis and increased migration of HCC-lines. Besides these pro-tumourigenic effects we could also observe tumouricidal properties of mesenchymal cells, as BLC-supernatants induced cell death of HCC-lines. Linoleic acid is an important source for hydroperoxides, which may be generated either endogenously in the course of inflammation or exogenously during food processing. We found that linoleic acid hydroperoxides (=LOOH) were able to activate mesenchymal cells of the liver resulting in the release of pro-inflammatory cytokines and growth factors including TNF-alpha (=tumour necrosis factor alpha) and HB-EGF (=heparin-binding epidermal growth factor-like growth factor), which turned out to be a growth factor for premalignant hepatocytes. Furthermore LOOH enhanced the growth of hepatocarcinoma cells via upregulation of the antiapoptotic enzyme heme oxygenase 1 and stimulation of cell proliferation. In conclusion, the results of our studies confirm the crucial role of different mesenchymal cells in early and late hepatocarcinogenesis and propose a tumour-promoting effect of LOOH. (author) [German] Bei hepatozellulaeren Karzinomen handelt es sich um Krebserkrankungen mit einer ausserordentlich hohen Sterblichkeit. Die wichtigsten Risikofaktoren sind chronische Hepatitis und die damit assoziierte Leberzirrhose als Folge von viralen Hepatitis-Infektionen, chronischem Alkoholkonsum oder Stoffwechselerkrankungen. Waehrend die stufenweise Pathogenese von Leberkrebs relativ gut untersucht wurde, ist die Rolle von mesenchymalen Zellen in der Hepatokarzinogenese weitgehend unbekannt. Fuer die Analyse epithelial-mesenchymaler Interaktionen in der spaeten Hepatokarzinogenese entwickelten wir neue Zelllinien aus menschlichen hepatozellulaeren Karzinomen: epitheliale (HCC)-, B-lymphoblastoide (BLC)- und myofibroblastoide (MF)-Linien. BLC-und MF-ueberstaende erhoehten die DNA-Replikation premaligner Hepatozyten, ueberstaende der MF-Linien foerderten sowohl Neoangiogenese als auch die Migration von HCC-Linien. Neben diesen pro-tumorigenen Effekten, konnten auch tumorizide Eigenschaften der mesenchymalen Zellen festgestellt werden, da BLC-ueberstaende den Zelltod von HCC-Linien induzierten. Linolsaeure ist eine wichtige Quelle fuer Hydroperoxide, die entweder endogen in Folge von entzuendlichen Prozessen oder exogen bei der Lebensmittelverarbeitung gebildet werden koennen. Wir haben beobachtet, dass Linolsaeurehydroperoxide (=LOOH) in der Lage sind Kupffer- und Endothelzellen zu aktivieren. Waehrend Kupffer-Zellen ueber die Sekretion von TNF-alpha (=tumour necrosis factor alpha) inflammatorische Prozesse verstaerken konnten, reagierten Endothelzellen vermehrt mit der Sekretion von HB-EGF (= heparin-binding epidermal growth factor-like growth factor), der sich als Wachstumsfaktor fuer premaligne Hepatozyten herausstellte. Ausserdem stimulierten LOOH das Wachstum von Leberkrebszellen, einerseits ueber die Induktion des antiapoptotischen Enzyms Haemoxygenase-1 und andererseits ueber die Anregung von Zellproliferation. Zusammenfassend bestaetigen die Ergebnisse unserer Studien die entscheidende Rolle von mesenchymalen Zellen in der fruehen und spaeten Hepatokarzinogenese und weisen auf eine tumorpromovierende Wirkung von LOOH hin. (author)}
place = {Austria}
year = {2009}
month = {Jul}
}
title = {Epithelial-mesenchymal interactions in early and late hepatocarcinogenesis with focus on the role of linoleic acid and its hydroperoxides}
author = {Sagmeister, S}
abstractNote = {Hepatocellular carcinomas are devastating cancers with high mortality rates. Major risk factors are chronic hepatitis and associated cirrhosis as consequence of viral hepatitis infections, chronically ethanol consumption or metabolic disorders. While the stepwise development of liver cancer is well investigated, the role of mesenchymal cells in this process is largely unknown. To analyse epithelial-mesenchymal interactions in advanced stages of hepatocarcinogenesis, we established new cell lines from human hepatocellular carcinomas and obtained several hepatocarcinoma (HCC)-, B-lymphoblastoid (BLC)- and myofibroblastoid (MF)-lines. BLC- and MF-supernatants were able to increase DNA replication of premalignant hepatocytes. Supernatants of MF-lines enhanced angiogenesis and increased migration of HCC-lines. Besides these pro-tumourigenic effects we could also observe tumouricidal properties of mesenchymal cells, as BLC-supernatants induced cell death of HCC-lines. Linoleic acid is an important source for hydroperoxides, which may be generated either endogenously in the course of inflammation or exogenously during food processing. We found that linoleic acid hydroperoxides (=LOOH) were able to activate mesenchymal cells of the liver resulting in the release of pro-inflammatory cytokines and growth factors including TNF-alpha (=tumour necrosis factor alpha) and HB-EGF (=heparin-binding epidermal growth factor-like growth factor), which turned out to be a growth factor for premalignant hepatocytes. Furthermore LOOH enhanced the growth of hepatocarcinoma cells via upregulation of the antiapoptotic enzyme heme oxygenase 1 and stimulation of cell proliferation. In conclusion, the results of our studies confirm the crucial role of different mesenchymal cells in early and late hepatocarcinogenesis and propose a tumour-promoting effect of LOOH. (author) [German] Bei hepatozellulaeren Karzinomen handelt es sich um Krebserkrankungen mit einer ausserordentlich hohen Sterblichkeit. Die wichtigsten Risikofaktoren sind chronische Hepatitis und die damit assoziierte Leberzirrhose als Folge von viralen Hepatitis-Infektionen, chronischem Alkoholkonsum oder Stoffwechselerkrankungen. Waehrend die stufenweise Pathogenese von Leberkrebs relativ gut untersucht wurde, ist die Rolle von mesenchymalen Zellen in der Hepatokarzinogenese weitgehend unbekannt. Fuer die Analyse epithelial-mesenchymaler Interaktionen in der spaeten Hepatokarzinogenese entwickelten wir neue Zelllinien aus menschlichen hepatozellulaeren Karzinomen: epitheliale (HCC)-, B-lymphoblastoide (BLC)- und myofibroblastoide (MF)-Linien. BLC-und MF-ueberstaende erhoehten die DNA-Replikation premaligner Hepatozyten, ueberstaende der MF-Linien foerderten sowohl Neoangiogenese als auch die Migration von HCC-Linien. Neben diesen pro-tumorigenen Effekten, konnten auch tumorizide Eigenschaften der mesenchymalen Zellen festgestellt werden, da BLC-ueberstaende den Zelltod von HCC-Linien induzierten. Linolsaeure ist eine wichtige Quelle fuer Hydroperoxide, die entweder endogen in Folge von entzuendlichen Prozessen oder exogen bei der Lebensmittelverarbeitung gebildet werden koennen. Wir haben beobachtet, dass Linolsaeurehydroperoxide (=LOOH) in der Lage sind Kupffer- und Endothelzellen zu aktivieren. Waehrend Kupffer-Zellen ueber die Sekretion von TNF-alpha (=tumour necrosis factor alpha) inflammatorische Prozesse verstaerken konnten, reagierten Endothelzellen vermehrt mit der Sekretion von HB-EGF (= heparin-binding epidermal growth factor-like growth factor), der sich als Wachstumsfaktor fuer premaligne Hepatozyten herausstellte. Ausserdem stimulierten LOOH das Wachstum von Leberkrebszellen, einerseits ueber die Induktion des antiapoptotischen Enzyms Haemoxygenase-1 und andererseits ueber die Anregung von Zellproliferation. Zusammenfassend bestaetigen die Ergebnisse unserer Studien die entscheidende Rolle von mesenchymalen Zellen in der fruehen und spaeten Hepatokarzinogenese und weisen auf eine tumorpromovierende Wirkung von LOOH hin. (author)}
place = {Austria}
year = {2009}
month = {Jul}
}