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

Rudolf Lucas, Roberto Montesano, Michael S. Pepper, Michael Hafner, Erwin Sablon, Yves Dunant, Georges E. Grau, Patrick De Baetselier, Daniela Mnnel, Lucie Fransen

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12 Scopus citations

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 anti-tumour activities, lectin-deficient TNF mutants might prove to be therapeutically interesting alternatives to wt TNF.

Original languageEnglish (US)
Pages (from-to)543-549
Number of pages7
JournalInternational Journal of Cancer
Volume91
Issue number4
DOIs
Publication statusPublished - Feb 15 2001
Externally publishedYes

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Keywords

  • Angiogenesis
  • Lectin
  • Metastasis
  • TNF
  • Therapy

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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