TNF-alpha mediated selection of macrophage-resistant gene-regulatory tumor variants.
Clin Exp Metastasis
; 7(5): 493-506, 1989.
Article
em En
| MEDLINE
| ID: mdl-2473862
ABSTRACT
In vitro macrophage- or TNF-alpha-mediated selection procedures on 3LL tumor cells have led to the selection of 3LL variants manifesting a highly reduced sensitivity towards the cytotoxic effects of both TNF-alpha and tumoricidal macrophages, while retaining the parental sensitivity to the cytolytic activity of (i) H2O2, (ii) macrophage-ADCC reactions and (iii) NK cells. A correlation was observed between the TNF-alpha binding capacity of the 3LL cell lines and their susceptibility towards macrophage- and TNF-alpha-mediated cytotoxicity, indicating that macrophage and TNF-alpha sensitivity may partially be regulated at the TNF-alpha receptor level. Further, the selected 3LL variants are gene-regulatory variants rather than cellular mutants, as upregulation of the TNF-alpha receptor by interferon-gamma (IFN-gamma) or 5'-azacytidine treatment resulted in an increased vulnerability of the selected 3LL variants to the killing activity of macrophages and TNF-alpha. The resistance of the 3LL variants to macrophage- and TNF-alpha-mediated cytotoxicity in vitro was reflected by a higher tumorigenic and metastatic potential in vivo. Therefore, the generation of TNF-alpha- and macrophage-resistant variants through immunoselection may contribute to the basic mechanisms of tumor progression and metastasis.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Fator de Necrose Tumoral alfa
/
Macrófagos
/
Neoplasias Experimentais
Limite:
Animals
Idioma:
En
Revista:
Clin Exp Metastasis
Assunto da revista:
NEOPLASIAS
Ano de publicação:
1989
Tipo de documento:
Article
País de afiliação:
Bélgica