Artikel
Significance of the anti-inflammatory factor hemeoxgenase-1 (HO-1) for the function of tumour infiltrating macrophages
Suche in Medline nach
Autoren
Veröffentlicht: | 20. März 2006 |
---|
Gliederung
Text
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.