Lucas, Rudolf and Montesano, Roberto and Pepper, Michael S. and Hafner, Michael and Sablon, Erwin and Dunant, Yves and Grau, Georges E. and De Baetselier, Patrick and Maennel, Daniela and Fransen, Lucie (2001) Lectin-deficient TNF mutants display comparable anti-tumour but reduced pro-metastatic potential as compared to the wild-type molecule. INTERNATIONAL JOURNAL OF CANCER, 91 (4). pp. 543-549. ISSN 0020-7136, 1097-0215
Full text not available from this repository. (Request a copy)Abstract
In this study, we characterised the anti-tumour as well as the pro-metastatic activities of TNF mutants deficient in their lectin-like activity.(16,19) We report that, despite reduced systemic toxicity as compared to wild-type (wt) mTNF, a (T104A) and a (T104A-E106A-E109A) mTNF mutant (triple mTNF) retained most of their necrotic and tumouristatic activities, as measured in a CFS-1 fibrosarcoma and a B16BL6 melanoma tumour model, respectively. These mutants also conserved their anti-angiogenic activity, as measured in an in vitro endothelial morphogenesis assay.(26) In contrast, the pro metastatic activity of the T104A and the triple mTNF mutants in the CFS-1 fibrosarcoma and the 3LL-R Lewis lung carcinoma tumour model was significantly lower than that of the wt molecule. These results thus indicate that the lectin-like domain of TNF is not implicated in its necrotic, tumouristatic and anti-angiogenic activities, but that it can contribute to the pro-metastatic effect of the cytokine. In conclusion, in view of their reduced systemic toxicity and pro-metastatic capacity, but their retained antitumour activities, lectin-deficient TNF mutants might prove to be therapeutically interesting alternatives to wt TNF. (C) 2001 Wiley-Liss, Inc.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | NECROSIS-FACTOR-ALPHA; MICROVASCULAR ENDOTHELIAL-CELLS; HUMAN-MELANOMA; INTERFERON-GAMMA; NUDE-MICE; IFN-GAMMA; INVITRO; RECEPTOR; GROWTH; ANGIOGENESIS; TNF; lectin; metastasis; angiogenesis; therapy |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Pathologie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 15 Feb 2022 06:44 |
| Last Modified: | 15 Feb 2022 06:44 |
| URI: | https://pred.uni-regensburg.de/id/eprint/41752 |
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