Orosz, P. and Echtenacher, Bernd and Falk, Werner and Rüschoff, J. and Weber, D. and Männel, Daniela N.
Enhancement of experimental metastasis by tumor necrosis factor.
The Journal of experimental medicine 177 (5), pp. 1391-1398.
The influence of endogenous and exogenous tumor necrosis factor (TNF) on metastasis was investigated in an experimental fibrosarcoma metastasis model. A single intraperitoneal injection of recombinant human (rh) TNF or recombinant mouse (rm) TNF into mice 5 h before intravenous inoculation of methylcholanthrene-induced fibrosarcoma cells (CFS1) induced a significant enhancement of the number of metastases in the lung. Dose responses of rmTNF and rhTNF demonstrated a stronger metastasis-augmenting effect by rmTNF compared with rhTNF. This effect was time dependent, as administration of rmTNF 5 h before or 1 h but not 24 h after tumor cell inoculation caused an increase of tumor cell colony formation on the lung surface, suggesting an influence of TNF on the vascular adhesion and diapedesis of tumor cells. Since tumor-bearing mice showed an enhanced ability to produce TNF after endotoxin injection compared to control mice, tumor-bearing mice were treated with anti-mTNF antibodies. Neutralization of endogenous tumor-induced TNF led to a significant decrease of the number of pulmonary metastases. Histological analysis of micrometastases in the lung on day 5 by silver staining of proteins associated with nucleolar organizer regions revealed more metastatic foci and augmented proliferative activity of the tumor cells after rmTNF pretreatment of mice. However, no direct effect of rmTNF on the proliferation rate of tumor cells was seen in vitro. These findings suggest that low doses of endogenous TNF or administered TNF during cytokine therapy might enhance the metastatic potential of circulating tumor cells.
|Institutions:|| Medicine > Lehrstuhl für Innere Medizin I|
Medicine > Lehrstuhl für Immunologie
|Endotoxins/administration & dosage||MESH|
|Mice, Inbred C3H||MESH|
|Mice, Inbred CBA||MESH|
|Tumor Cells, Cultured||MESH|
|Tumor Necrosis Factor-alpha/physiology||MESH|
|Subjects:||600 Technology > 610 Medical sciences Medicine|
|Refereed:||Yes, this version has been refereed|
|Created at the University of Regensburg:||Unknown|
|Deposited On:||08 Sep 2010 05:14|
|Last Modified:||20 Jul 2011 22:36|