gms | German Medical Science

27th German Cancer Congress Berlin 2006

German Cancer Society (Frankfurt/M.)

22. - 26.03.2006, Berlin

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Significance of the anti-inflammatory factor hemeoxgenase-1 (HO-1) for the function of tumour infiltrating macrophages

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  • corresponding author presenting/speaker Christoph Benckert - Charité, Universitätsmedizin Berlin, Campus Virchow Klinikum,Med. Klinik mit Schwerpunkt Hepatologie u. Gastroenterologie, Berlin
  • Nadine Rohwer - Charité, Universitätsmedizin Berlin, Campus Virchow Klinikum,Med. Klinik mit Schwerpunkt Hepatologie u. Gastroenterologie
  • Thorsten Cramer - Charité, Universitätsmedizin Berlin, Campus Virchow Klinikum,Med. Klinik mit Schwerpunkt Hepatologie u. Gastroenterologie
  • Antonino Spinelli - Charité, Universitätsmedizin Berlin, Campus Virchow Klinikum, Klinik f. Allgemein- Viszeral- u. Transplantationschirurgie, Berlin
  • Peter Neuhaus - Charité, Universitätsmedizin Berlin, Campus Virchow Klinikum, Klinik f. Allgemein- Viszeral- u. Transplantationschirurgie, Berlin
  • Sven Jonas - Charité, Universitätsmedizin Berlin, Campus Virchow Klinikum, Klinik f. Allgemein- Viszeral- u. Transplantationschirurgie, Berlin

27. Deutscher Krebskongress. Berlin, 22.-26.03.2006. Düsseldorf, Köln: German Medical Science; 2006. DocPO217

The electronic version of this article is the complete one and can be found online at: http://www.egms.de/en/meetings/dkk2006/06dkk327.shtml

Published: March 20, 2006

© 2006 Benckert et al.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by-nc-nd/3.0/deed.en). You are free: to Share – to copy, distribute and transmit the work, provided the original author and source are credited.

Outline

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Introduction: The infiltration of various tumours with macrophages is associated with a higher rate of metastasis and a poor prognosis. The underlying mechanisms are widely unknown. Hemeoygenase-1 (HO-1) is expressed in macrophages and acts predominantly anti-inflammatory and anti-oxidative. The significance of HO-1 for the migration of macrophages and the accumulation in tissues has not been investigated so far.

Methods: The in vivo expression of HO-1 was determined by Immunohistochemistry in 60 human HCCs. In vitro expression and of HO-1 activity were measured by western blot and real time PCR in the human monocyte cell line THP-1. Migration was analysed in THP-1 cells in Boyden chamber invasion assays.

Results: HO-1 was detected immunohistochemically in peritumorous HCC tissue andkupfer cells in 45 out of 60 (85%) tumour specimens. HO-1 protein and RNA could not be detected in THP-1 cells under normal conditions. Stimulation by oxidative stress leads to a highly significant stimulation of the HO-1 RNA and protein expression (150-fold). Induction of the HO-1 activity by haemin resulted in a significant decrease of the migration of THP-1 cells. Otherwise, inhibition of the HO-1 activity by Sn-protoporphyrin resulted in a significantly higher migration rate of THP-1 cells.

Discussion: For the first time we could demonstrate the exclusive expression of HO-1 in human HCCtumourspecimen by macrophages and/or kupfer cells and confirm data shown by other groups in animal HCC models. Inhibition of the migration of macrophages by HO-1 activation adverts to a central role of HO-1 for the accumulation of macrophages in human HCC. Further studies should investigate whether HO-1 inhibition may reduce HCC tumour growth.