en
Scientific article
English

Lectin-deficient TNF mutants display comparable anti-tumour but reduced pro-metastatic potential as compared to the wild-type molecule

Published inInternational journal of cancer, vol. 91, no. 4, p. 543-549
Publication date2001
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.1619 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 anti-tumour activities, lectin-deficient TNF mutants might prove to be therapeutically interesting alternatives to wt TNF.

Keywords
  • Animals
  • Carcinoma, Lewis Lung
  • Cattle
  • Cell Adhesion
  • Collagen/metabolism
  • Dose-Response Relationship, Drug
  • Endothelium, Vascular/cytology/metabolism
  • Female
  • Fibrosarcoma/genetics/metabolism
  • Lectins/metabolism
  • Lung/metabolism
  • Melanoma, Experimental/genetics/metabolism
  • Mice
  • Mice, Inbred C3H
  • Mice, Inbred C57BL
  • Mutation
  • Necrosis
  • Neoplasm Metastasis
  • Neoplasm Transplantation
  • Neoplasms, Experimental
  • Neovascularization, Pathologic
  • Protein Structure, Tertiary
  • Recombinant Proteins/metabolism
  • Time Factors
  • Tumor Cells, Cultured
  • Tumor Necrosis Factor-alpha/chemistry/genetics/therapeutic use
Citation (ISO format)
LUCAS, Rudolf et al. Lectin-deficient TNF mutants display comparable anti-tumour but reduced pro-metastatic potential as compared to the wild-type molecule. In: International journal of cancer, 2001, vol. 91, n° 4, p. 543–549. doi: 10.1002/1097-0215(200002)9999:9999<::aid-ijc1090>3.0.co;2-y
Main files (1)
Article (Accepted version)
accessLevelRestricted
ISSN of the journal0020-7136
513views
0downloads

Technical informations

Creation10/22/2009 3:49:00 PM
First validation10/22/2009 3:49:00 PM
Update time03/14/2023 3:16:41 PM
Status update03/14/2023 3:16:41 PM
Last indexation01/15/2024 7:08:33 PM
All rights reserved by Archive ouverte UNIGE and the University of GenevaunigeBlack